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Dietary patterns in relation to glioma: a case–control study Cancer Metab. (IF 5.9) Pub Date : 2024-03-18 Mohammad Nemati, Mehdi Shayanfar, Fatemeh Almasi, Minoo Mohammad-Shirazi, Giuve Sharifi, Azadeh Aminianfar, Ahmad Esmaillzadeh
Although the association of individual foods and nutrients with glioma have been investigated, studies on the association of major dietary patterns and glioma are scarce. The aim of this study was to examine the association between major dietary patterns and risk of glioma in a group of Iranian adults. In this hospital-based case–control design, we recruited 128 newly diagnosed glioma cases and 256
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Elevated expression of HIGD1A drives hepatocellular carcinoma progression by regulating polyamine metabolism through c-Myc–ODC1 nexus Cancer Metab. (IF 5.9) Pub Date : 2024-02-23 Haixing Zhang, Xiaoran Li, Ziying Liu, Zimo Lin, Kuiyuan Huang, Yiran Wang, Yu Chen, Leyi Liao, Leyuan Wu, Zhanglian Xie, Jinlin Hou, Xiaoyong Zhang, Hongyan Liu
Hypoxia contributes to cancer progression through various molecular mechanisms and hepatocellular carcinoma (HCC) is one of the most hypoxic malignancies. Hypoxia-inducible gene domain protein-1a (HIGD1A) is typically induced via epigenetic regulation and promotes tumor cell survival during hypoxia. However, the role of HIGD1A in HCC remains unknown. HIGD1A expression was determined in 24 pairs of
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High-fat diet promotes prostate cancer metastasis via RPS27 Cancer Metab. (IF 5.9) Pub Date : 2024-02-16 Dameng Li, Xueying Zhou, Wenxian Xu, Yongxin Cai, Chenglong Mu, Xinchun Zhao, Tingting Tang, Chen Liang, Tao Yang, Junnian Zheng, Liang Wei, Bo Ma
Metastasis is the leading cause of death among prostate cancer (PCa) patients. Obesity is associated with both PCa-specific and all-cause mortality. High-fat diet (HFD) is a risk factor contributing to obesity. However, the association of HFD with PCa metastasis and its underlying mechanisms are unclear. Tumor xenografts were conducted by intrasplenic injections. The ability of migration or invasion
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Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response Cancer Metab. (IF 5.9) Pub Date : 2024-02-13 Ceren Yalaz, Esther Bridges, Nasullah K. Alham, Christos E. Zois, Jianzhou Chen, Karim Bensaad, Ana Miar, Elisabete Pires, Ruth J. Muschel, James S. O. McCullagh, Adrian L. Harris
PDE6H encodes PDE6γ′, the inhibitory subunit of the cGMP-specific phosphodiesterase 6 in cone photoreceptors. Inhibition of PDE6, which has been widely studied for its role in light transduction, increases cGMP levels. The purpose of this study is to characterise the role of PDE6H in cancer cell growth. From an siRNA screen for 487 genes involved in metabolism, PDE6H was identified as a controller
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Circulating metabolome landscape in Lynch syndrome Cancer Metab. (IF 5.9) Pub Date : 2024-02-05 Tiina A. Jokela, Jari E. Karppinen, Minta Kärkkäinen, Jukka-Pekka Mecklin, Simon Walker, Toni T. Seppälä, Eija K. Laakkonen
Circulating metabolites systemically reflect cellular processes and can modulate the tissue microenvironment in complex ways, potentially impacting cancer initiation processes. Genetic background increases cancer risk in individuals with Lynch syndrome; however, not all carriers develop cancer. Various lifestyle factors can influence Lynch syndrome cancer risk, and lifestyle choices actively shape
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Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia Cancer Metab. (IF 5.9) Pub Date : 2024-01-25 Guo-Tian Ruan, Li Deng, Hai-Lun Xie, Jin-Yu Shi, Xiao-Yue Liu, Xin Zheng, Yue Chen, Shi-Qi Lin, He-Yang Zhang, Chen-An Liu, Yi-Zhong Ge, Meng-Meng Song, Chun-Lei Hu, Xiao-Wei Zhang, Ming Yang, Wen Hu, Ming-Hua Cong, Li-Chen Zhu, Kun-Hua Wang, Han-Ping Shi
The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. In this study, our prospective
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Deficiency of TOP1MT enhances glycolysis through the stimulation of PDK4 expression in gastric cancer Cancer Metab. (IF 5.9) Pub Date : 2024-01-10 Hongqiang Wang, Xutao Sun, Chen Yang, Ziqi Li, Danwen Jin, Wenwen Zhu, Ze Yu
Abnormal glucose metabolism is one of the determinants of maintaining malignant characteristics of cancer. Targeting cancer metabolism is regarded as a new strategy for cancer treatment. Our previous studies have found that TOP1MT is a crucial gene that inhibits glycolysis and cell metastasis of gastric cancer (GC) cells, but the mechanism of its regulation of glycolysis remains unclear. Transcriptome
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Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer Cancer Metab. (IF 5.9) Pub Date : 2024-01-02 Federica Tambaro, Giovanni Imbimbo, Elisabetta Ferraro, Martina Andreini, Roberta Belli, Maria Ida Amabile, Cesarina Ramaccini, Giulia Lauteri, Giuseppe Nigri, Maurizio Muscaritoli, Alessio Molfino
Adipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy. For this reason, we assessed the expression of the lipolysis-associated genes and proteins in subcutaneous adipose tissue (SAT) of gastrointestinal (GI) cancer patients compared to controls to verify their involvement in cancer, among different
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A feedback loop of PPP and PI3K/AKT signal pathway drives regorafenib-resistance in HCC Cancer Metab. (IF 5.9) Pub Date : 2023-12-18 Huihua Yang, Dahong Chen, Yafei Wu, Heming Zhou, Wenjing Diao, Gaolin Liu, Qin Li
Hepatocellular carcinoma (HCC) is a principal type of liver cancer with high incidence and mortality rates. Regorafenib is a novel oral multikinase inhibitor for second-line therapy for advanced HCC. However, resistance to regorafenib is gradually becoming a dilemma for HCC and the mechanism remains unclear. In this study, we aimed to reveal the metabolic profiles of regorafenib-resistant cells and
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STEAP4 inhibits cisplatin-induced chemotherapy resistance through suppressing PI3K/AKT in hepatocellular carcinoma Cancer Metab. (IF 5.9) Pub Date : 2023-12-18 Binhui Xie, Baiyin Zhong, Zhenxian Zhao, Jie Hu, Jianqiong Yang, Yuankang Xie, Jianhong Zhang, Jianting Long, Xuewei Yang, Heping Li
Chemotherapy resistance is the leading cause for hepatocellular carcinoma (HCC)-induced death. Exploring resistance generation mechanism is an urgent need for HCC therapy. Here, we found STEAP4 was significantly downregulated in HCC patients with recurrence. Patients with low STEAP4 had poor outcome, suggesting STEAP4 might inhibit chemotherapy resistance. Cell viability assay, colony formation assay
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A HIF-1α inhibitor combined with palmitic acid and L-carnitine treatment can prevent the fat metabolic reprogramming under hypoxia and induce apoptosis in hepatocellular carcinoma cells Cancer Metab. (IF 5.9) Pub Date : 2023-12-08 Shohei Matsufuji, Yoshihiko Kitajima, Kazuki Higure, Naoya Kimura, Sachiko Maeda, Kohei Yamada, Kotaro Ito, Tomokazu Tanaka, Keita Kai, Hirokazu Noshiro
A hypoxic environment often persists within solid tumors, including hepatocellular carcinoma (HCC). Hypoxia-inducible factor-1α (HIF-1α) can accelerate cancer malignancy by inducing hypoxia-dependent expression of various genes. Tumor hypoxia can also induce metabolic reprogramming of fatty acid (FA) metabolism, through which HIF-1α plays an essential role in diminishing fatty acid β-oxidation (FAO)
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The classification of obesity based on metabolic status redefines the readmission of non-Hodgkin’s lymphoma—an observational study Cancer Metab. (IF 5.9) Pub Date : 2023-12-06 Hang Dong, Honglin Guo, Jing Du, Yiping Cheng, Dawei Wang, Junming Han, Zinuo Yuan, Zhenyu Yao, Ran An, Xiaoqin Wu, Kyle L. Poulsen, Zhixiang Wang, Shanshan Shao, Xiude Fan, Zhen Wang, Jiajun Zhao
The relationship between obesity and non-Hodgkin’s lymphoma (NHL) was controversial, which may be due to the crudeness definition of obesity based on body mass index (BMI). As obesity and metabolic abnormalities often coexist, we aimed to explore whether the classification of obesity based on metabolic status can help to evaluate the real impact of obesity on the readmission of NHL. In this retrospective
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Metabolic changes preceding bladder cancer occurrence among Korean men: a nested case-control study from the KCPS-II cohort Cancer Metab. (IF 5.9) Pub Date : 2023-12-05 Youngmin Han, Unchong Kim, Keum Ji Jung, Ji-Young Lee, Kwangbae Lee, Sang Yop Shin, Heejin Kimm, Sun Ha Jee
Bladder cancer (BLCA) research in Koreans is still lacking, especially in focusing on the prediction of BLCA. The current study aimed to discover metabolic signatures related to BLCA onset and confirm its potential as a biomarker. We designed two nested case-control studies using Korean Cancer Prevention Study (KCPS)-II. Only males aged 35–69 were randomly selected and divided into two sets by recruitment
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Autofluorescence imaging of endogenous metabolic cofactors in response to cytokine stimulation of classically activated macrophages Cancer Metab. (IF 5.9) Pub Date : 2023-11-13 Shelby N. Bess, Matthew J. Igoe, Abby C. Denison, Timothy J. Muldoon
Macrophages are one of the most prevalent subsets of immune cells within the tumor microenvironment and perform a range of functions depending on the cytokines and chemokines released by surrounding cells and tissues. Recent research has revealed that macrophages can exhibit a spectrum of phenotypes, making them highly plastic due to their ability to alter their physiology in response to environmental
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The effects of chemotherapy on resting energy expenditure, body composition, and cancer-related fatigue in women with breast cancer: a prospective cohort study Cancer Metab. (IF 5.9) Pub Date : 2023-11-09 Timia Van Soom, Wiebren Tjalma, Konstantinos Papadimitriou, Nick Gebruers, Eric van Breda
Breast cancer (BC) is the most prevalent tumor in women. Improvements in treatment led to declined mortality, resulting in more survivors living with cancer- or therapy-induced comorbidities. In this study, we investigated the impact of neoplasia and chemotherapy on resting energy expenditure (REE) and body composition, in relation to cancer-related fatigue. Inflammatory parameters were checked as
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ATM inhibition blocks glucose metabolism and amplifies the sensitivity of resistant lung cancer cell lines to oncogene driver inhibitors Cancer Metab. (IF 5.9) Pub Date : 2023-11-06 Cristina Terlizzi, Viviana De Rosa, Francesca Iommelli, Antonio Pezone, Giovanna G. Altobelli, Maurizio Maddalena, Jelena Dimitrov, Caterina De Rosa, Carminia Maria Della Corte, Vittorio Enrico Avvedimento, Silvana Del Vecchio
ATM is a multifunctional serine/threonine kinase that in addition to its well-established role in DNA repair mechanisms is involved in a number of signaling pathways including regulation of oxidative stress response and metabolic diversion of glucose through the pentose phosphate pathway. Oncogene-driven tumorigenesis often implies the metabolic switch from oxidative phosphorylation to glycolysis which
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Correction: Cholesterol reprograms glucose and lipid metabolism to promote proliferation in colon cancer cells Cancer Metab. (IF 5.9) Pub Date : 2023-10-26 Shyamananda Singh Mayengbam, Abhijeet Singh, Himanshi Yaduvanshi, Firoz Khan Bhati, Bhavana Deshmukh, Dipti Athavale, Pranay L. Ramteke, Manoj Kumar Bhat
Correction: Cancer & Metabolism 11, 15 (2023) https://doi.org/10.1186/s40170-023-00315-1 Following publication of the original article [1], it came to the author's attention that there were two errors in the figures and supplementary files of the article: 1) In Fig. 6, panel D, the MCT-2 blot in the presence of LDL and HDL had been inadvertently duplicated; for ESM 2, the wrong file (‘Supplementary
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Aspirin reprogrammes colorectal cancer cell metabolism and sensitises to glutaminase inhibition Cancer Metab. (IF 5.9) Pub Date : 2023-10-19 Amy K. Holt, Arafath K. Najumudeen, Tracey J. Collard, Hao Li, Laura M. Millett, Ashley J. Hoskin, Danny N. Legge, Eleanor M. H. Mortensson, Dustin J. Flanagan, Nicholas Jones, Madhu Kollareddy, Penny Timms, Matthew D. Hitchings, James Cronin, Owen J. Sansom, Ann C. Williams, Emma E. Vincent
To support proliferation and survival within a challenging microenvironment, cancer cells must reprogramme their metabolism. As such, targeting cancer cell metabolism is a promising therapeutic avenue. However, identifying tractable nodes of metabolic vulnerability in cancer cells is challenging due to their metabolic plasticity. Identification of effective treatment combinations to counter this is
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Untargeted plasma metabolomics and risk of colorectal cancer—an analysis nested within a large-scale prospective cohort Cancer Metab. (IF 5.9) Pub Date : 2023-10-17 Linda Vidman, Rui Zheng, Stina Bodén, Anton Ribbenstedt, Marc J. Gunter, Richard Palmqvist, Sophia Harlid, Carl Brunius, Bethany Van Guelpen
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, but if discovered at an early stage, the survival rate is high. The aim of this study was to identify novel markers predictive of future CRC risk using untargeted metabolomics. This study included prospectively collected plasma samples from 902 CRC cases and 902 matched cancer-free control participants from the population-based
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Identification of predictive biomarkers for endometrial cancer diagnosis and treatment response monitoring using plasma metabolome profiling Cancer Metab. (IF 5.9) Pub Date : 2023-10-11 Eiji Hishinuma, Muneaki Shimada, Naomi Matsukawa, Yoshiko Shima, Bin Li, Ikuko N. Motoike, Yusuke Shibuya, Tatsuya Hagihara, Shogo Shigeta, Hideki Tokunaga, Daisuke Saigusa, Kengo Kinoshita, Seizo Koshiba, Nobuo Yaegashi
Endometrial cancer (EMC) is the most common female genital tract malignancy with an increasing prevalence in many countries including Japan, a fact that renders early detection and treatment necessary to protect health and fertility. Although early detection and treatment are necessary to further improve the prognosis of women with endometrial cancer, biomarkers that accurately reflect the pathophysiology
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Cholesterol reprograms glucose and lipid metabolism to promote proliferation in colon cancer cells Cancer Metab. (IF 5.9) Pub Date : 2023-09-13 Shyamananda Singh Mayengbam, Abhijeet Singh, Himanshi Yaduvanshi, Firoz Khan Bhati, Bhavana Deshmukh, Dipti Athavale, Pranay L. Ramteke, Manoj Kumar Bhat
Hypercholesterolemia is often correlated with obesity which is considered a risk factor for various cancers. With the growing population of hypercholesterolemic individuals, there is a need to understand the role of increased circulatory cholesterol or dietary cholesterol intake towards cancer etiology and pathology. Recently, abnormality in the blood cholesterol level of colon cancer patients has
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Positron emission tomography imaging of the sodium iodide symporter senses real-time energy stress in vivo Cancer Metab. (IF 5.9) Pub Date : 2023-09-07 Piotr Dzien, Agata Mackintosh, Gaurav Malviya, Emma Johnson, Dmitry Soloviev, Gavin Brown, Alejandro Huerta Uribe, Colin Nixon, Scott K. Lyons, Oliver Maddocks, Karen Blyth, David Y. Lewis
Tissue environment is critical in determining tumour metabolic vulnerability. However, in vivo drug testing is slow and waiting for tumour growth delay may not be the most appropriate endpoint for metabolic treatments. An in vivo method for measuring energy stress would rapidly determine tumour targeting in a physiologically relevant environment. The sodium-iodide symporter (NIS) is an imaging reporter
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Comparative polar and lipid plasma metabolomics differentiate KSHV infection and disease states Cancer Metab. (IF 5.9) Pub Date : 2023-08-31 Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec
Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA)
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Magnetospirillum magneticum triggers apoptotic pathways in human breast cancer cells Cancer Metab. (IF 5.9) Pub Date : 2023-08-09 Stefano Menghini, Matej Vizovisek, Jonathas Enders, Simone Schuerle
The use of bacteria in cancer immunotherapy has the potential to bypass many shortcomings of conventional treatments. The ability of anaerobic bacteria to preferentially accumulate and replicate in hypoxic regions of solid tumors, as a consequence of bacterial metabolic needs, is particularly advantageous and key to boosting their immunostimulatory therapeutic actions in situ. While several of these
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Restoring gluconeogenesis by TEF inhibited proliferation and promoted apoptosis and immune surveillance in kidney renal clear cell carcinoma Cancer Metab. (IF 5.9) Pub Date : 2023-08-08 Wenyuan Zhuang, Xiaokai Shi, Shenglin Gao, Xihu Qin
Kidney renal clear cell carcinoma (KIRC) is the major histological subtype of kidney tumor which covers approximately 80% of the cases. Although various therapies have been developed, the clinical outcome remains unsatisfactory. Metabolic dysregulation is a key feature of KIRC, which impacts progression and prognosis of the disease. Therefore, understanding of the metabolic changes in KIRC is of great
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Long non-coding RNA CCHE1 modulates LDHA-mediated glycolysis and confers chemoresistance to melanoma cells Cancer Metab. (IF 5.9) Pub Date : 2023-07-21 Zhi Ding, Junyi Yang, Baojin Wu, Yingzhi Wu, Fanli Guo
Melanoma is considered as the most common metastatic skin cancer with increasing incidence and high mortality globally. The vital roles of long non-coding RNAs (lncRNAs) in the tumorigenesis of melanoma are elucidated by emerging evidence. The lncRNA cervical carcinoma high-expressed 1 (CCHE1) was overexpressed and acted as an oncogene in a variety of cancers, while the function of CCHE1 in melanoma
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BMP4 upregulates glycogen synthesis through the SMAD/SLC2A1 (GLUT1) signaling axis in hepatocellular carcinoma (HCC) cells Cancer Metab. (IF 5.9) Pub Date : 2023-07-13 Jiamin Zhong, Luyao Tian, Yannian Gou, Piao Zhao, Xiangyu Dong, Meichun Guo, Guozhi Zhao, Aohua Li, Ailing Hao, Tong-Chuan He, Jiaming Fan
Excessive hepatic glycogen accumulation benefits tumorigenesis and cancer cell survival. We previously reported that BMP4 has the strongest ability to promote glycogenesis among the 14 BMPs in hepatocytes and augmented hepatocellular carcinoma (HCC) cell survival under hypoxia and hypoglycemia conditions by promoting the glycolysis pathway. However, the mechanism underlying BMP4’s effect on glycogenesis
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Obesity and breast cancer prognosis: pre-diagnostic anthropometric measures in relation to patient, tumor, and treatment characteristics Cancer Metab. (IF 5.9) Pub Date : 2023-06-27 Sixten Harborg, Maria Feldt, Deirdre Cronin-Fenton, Marie Klintman, Susanne O. Dalton, Ann H. Rosendahl, Signe Borgquist
Examine the association between obesity and clinical outcomes in early breast cancer and assess if patient, tumor, and treatment characteristics modify such associations in Malmö Diet and Cancer Study patients (MDCS). The MDCS enrolled 17,035 Swedish women from 1991 to 1996. At enrollment, participants' body mass index (BMI), waist circumference and body fat percentage measures were collected. We identified
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Dual inhibition of IDO1/TDO2 enhances anti-tumor immunity in platinum-resistant non-small cell lung cancer Cancer Metab. (IF 5.9) Pub Date : 2023-05-24 Chunjing Wu, Sydney A. Spector, George Theodoropoulos, Dan J. M. Nguyen, Emily Y. Kim, Ashley Garcia, Niramol Savaraj, Diane C. Lim, Ankita Paul, Lynn G. Feun, Michael Bickerdike, Medhi Wangpaichitr
The impact of non-small cell lung cancer (NSCLC) metabolism on the immune microenvironment is not well understood within platinum resistance. We have identified crucial metabolic differences between cisplatin-resistant (CR) and cisplatin-sensitive (CS) NSCLC cells with elevated indoleamine 2,3-dioxygenase-1 (IDO1) activity in CR, recognized by increased kynurenine (KYN) production. Co-culture, syngeneic
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Safety, tolerability, and effectiveness of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in combination with standard chemotherapy for patients with advanced, inoperable pancreatic adenocarcinoma: a phase 1b observational study Cancer Metab. (IF 5.9) Pub Date : 2023-05-18 Lauren K. Park, Kian-Huat Lim, Jonas Volkman, Mina Abdiannia, Hannah Johnston, Zack Nigogosyan, Marilyn J. Siegel, Janet B. McGill, Alexis M. McKee, Maamoun Salam, Rong M. Zhang, Da Ma, Karteek Popuri, Vincent Tze Yang Chow, Mirza Faisal Beg, William G. Hawkins, Linda R. Peterson, Joseph E. Ippolito
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Thus, there is an urgent need for safe and effective novel therapies. PDAC’s excessive reliance on glucose metabolism for its metabolic needs provides a target for metabolic therapy. Preclinical PDAC models have demonstrated that targeting the sodium-glucose co-transporter-2 (SGLT2) with dapagliflozin may be a novel strategy. Whether dapagliflozin
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Normalization of hepatic ChREBP activity does not protect against liver disease progression in a mouse model for Glycogen Storage Disease type Ia Cancer Metab. (IF 5.9) Pub Date : 2023-04-21 Martijn G. S. Rutten, Yu Lei, Joanne H. Hoogerland, Vincent W. Bloks, Hong Yang, Trijnie Bos, Kishore A. Krishnamurthy, Aycha Bleeker, Mirjam H. Koster, Rachel E. Thomas, Justina C. Wolters, Hilda van den Bos, Gilles Mithieux, Fabienne Rajas, Adil Mardinoglu, Diana C. J. Spierings, Alain de Bruin, Bart van de Sluis, Maaike H. Oosterveer
Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by a defect in glucose-6-phosphatase (G6PC1) activity, which induces severe hepatomegaly and increases the risk for liver cancer. Hepatic GSD Ia is characterized by constitutive activation of Carbohydrate Response Element Binding Protein (ChREBP), a glucose-sensitive transcription factor. Previously, we showed that ChREBP
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Breast cancer cells that preferentially metastasize to lung or bone are more glycolytic, synthesize serine at greater rates, and consume less ATP and NADPH than parent MDA-MB-231 cells Cancer Metab. (IF 5.9) Pub Date : 2023-02-20 Mika B. Jekabsons, Mollie Merrell, Anna G. Skubiz, Noah Thornton, Sandra Milasta, Douglas Green, Taosheng Chen, Yan-Hong Wang, Bharathi Avula, Ikhlas A. Khan, Yu-Dong Zhou
Gene expression signatures associated with breast cancer metastases suggest that metabolic re-wiring is important for metastatic growth in lungs, bones, and other organs. However, since pathway fluxes depend on additional factors such as ATP demand, allosteric effects, and post-translational modification, flux analysis is necessary to conclusively establish phenotypes. In this study, the metabolic
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Tamoxifen induces radioresistance through NRF2-mediated metabolic reprogramming in breast cancer Cancer Metab. (IF 5.9) Pub Date : 2023-02-08 F. V. Naumann, F. C. G. J. Sweep, G. J. Adema, W. J. M. Peeters, J. W. M. Martens, J. Bussink, P. N. Span
Recently, we reported that tamoxifen-resistant (TAM-R) breast cancer cells are cross-resistant to irradiation. Here, we investigated the mechanisms associated with tamoxifen-induced radioresistance, aiming to prevent or reverse resistance and improve breast cancer treatment. Wild-type ERα-positive MCF7 and ERα-negative MDA-MB-231 breast cancer cells and their TAM-R counterparts were analyzed for cellular
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Metabolic profiling reveals metabolic features of consolidation therapy in pediatric acute lymphoblastic leukemia Cancer Metab. (IF 5.9) Pub Date : 2023-01-23 Jinqiu Fu, Aijun Zhang, Qinqin Liu, Dong Li, Xiaoming Wang, Libo Si
Acute lymphoblastic leukemia (ALL) and its treatment continue to pose substantial risks. To understand ALL more deeply, the metabolome in fasting plasma of 27 ALL patients before and after high-dose methotrexate therapies (consolidation therapy) including methotrexate and 6-mercaptopurine (6-MP) was investigated. Plasma metabolites were analyzed using liquid chromatography–tandem mass spectrometry
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Arginase-1 inhibition reduces migration ability and metastatic colonization of colon cancer cells Cancer Metab. (IF 5.9) Pub Date : 2023-01-13 Wang, Xiangdong, Xiang, Huihui, Toyoshima, Yujiro, Shen, Weidong, Shichi, Shunsuke, Nakamoto, Hiroki, Kimura, Saori, Sugiyama, Ko, Homma, Shigenori, Miyagi, Yohei, Taketomi, Akinobu, Kitamura, Hidemitsu
Arginase-1 (ARG1), a urea cycle-related enzyme, catalyzes the hydrolysis of arginine to urea and ornithine, which regulates the proliferation, differentiation, and function of various cells. However, it is unclear whether ARG1 controls the progression and malignant alterations of colon cancer. We established metastatic colonization mouse model and ARG1 overexpressing murine colon cancer CT26 cells
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Functional noninvasive detection of glycolytic pancreatic ductal adenocarcinoma Cancer Metab. (IF 5.9) Pub Date : 2022-12-09 Heid, Irina, Münch, Corinna, Karakaya, Sinan, Lueong, Smiths S., Winkelkotte, Alina M., Liffers, Sven T., Godfrey, Laura, Cheung, Phyllis F. Y., Savvatakis, Konstantinos, Topping, Geoffrey J., Englert, Florian, Kritzner, Lukas, Grashei, Martin, Tannapfel, Andrea, Viebahn, Richard, Wolters, Heiner, Uhl, Waldemar, Vangala, Deepak, Smeets, Esther M. M., Aarntzen, Erik H. J. G., Rauh, Daniel, Weichert
Pancreatic ductal adenocarcinoma (PDAC) lacks effective treatment options beyond chemotherapy. Although molecular subtypes such as classical and QM (quasi-mesenchymal)/basal-like with transcriptome-based distinct signatures have been identified, deduced therapeutic strategies and targets remain elusive. Gene expression data show enrichment of glycolytic genes in the more aggressive and therapy-resistant
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PDK1- and PDK2-mediated metabolic reprogramming contributes to the TGFβ1-promoted stem-like properties in head and neck cancer Cancer Metab. (IF 5.9) Pub Date : 2022-12-06 Sun, Wan-Hsuan, Chen, Yun-Hsuan, Lee, Hou-Hsuan, Tang, Yu-Wen, Sun, Kuang-Hui
Resistance to chemotherapeutic drugs is a key factor for cancer recurrence and metastases in head and neck cancer (HNC). Cancer stem cells (CSCs) in tumors have self-renewal, differentiation, and higher drug resistance capabilities, resulting in a poor prognosis for patients. In glucose metabolism, pyruvate dehydrogenase kinase (PDK) inhibits pyruvate dehydrogenase and impedes pyruvate from being metabolized
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Tadalafil increases the antitumor activity of 5-FU through inhibiting PRMT5-mediated glycolysis and cell proliferation in colorectal cancer Cancer Metab. (IF 5.9) Pub Date : 2022-12-06 Shen, Yao, Zhao, Pan, Dong, Kewei, Wang, Jiajia, Li, Huichen, Li, Mengyang, Li, Ruikai, Chen, Suning, Shen, Yuxia, Liu, Zhiyu, Xie, Mianjiao, Shen, Peng, Zhang, Jian
Protein arginine methyltransferase 5 (PRMT5) is upregulated in multiple tumors and plays a pivotal role in cancer cell proliferation. However, the role of PRMT5 in colorectal cancer remains poorly understood. We detected the expression level of PRMT5 and glycolytic enzymes using online databases and colorectal cancer cell lines by immunohistochemical staining, quantitative real-time polymerase chain
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Isotope tracing reveals distinct substrate preference in murine melanoma subtypes with differing anti-tumor immunity Cancer Metab. (IF 5.9) Pub Date : 2022-12-01 Zhang, Xinyi, Halberstam, Alexandra A., Zhu, Wanling, Leitner, Brooks P., Thakral, Durga, Bosenberg, Marcus W., Perry, Rachel J.
Research about tumor “metabolic flexibility”—the ability of cells to toggle between preferred nutrients depending on the metabolic context—has largely focused on obesity-associated cancers. However, increasing evidence for a key role for nutrient competition in the tumor microenvironment, as well as for substrate regulation of immune function, suggests that substrate metabolism deserves reconsideration
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Blocking lncRNA-SNHG16 sensitizes gastric cancer cells to 5-Fu through targeting the miR-506-3p-PTBP1-mediated glucose metabolism Cancer Metab. (IF 5.9) Pub Date : 2022-11-29 Ding, Yan, Gao, Sujie, Zheng, Jiabin, Chen, Xuebo
Gastric cancer (GC) is a commonly occurring human malignancy. The 5-fluorouracil (5-Fu) is a first-line anti-gastric cancer agent. However, a large number of GC patients developed 5-Fu resistance. Currently, the roles and molecular mechanisms of the lncRNA-SNHG16-modulated 5-Fu resistance in gastric cancer remain elusive. Expressions of lncRNA, miRNA, and mRNA were detected by qRT-PCR and Western blot
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Computed tomography-measured body composition and survival in rectal cancer patients: a Swedish cohort study Cancer Metab. (IF 5.9) Pub Date : 2022-11-23 Kotti, Angeliki, Holmqvist, Annica, Woisetschläger, Mischa, Sun, Xiao-Feng
The association between body composition and survival in rectal cancer patients is still unclear. Therefore, we aimed to evaluate the impact of computed tomography (CT)-measured body composition on survival in rectal cancer patients, stratifying our analyses by sex, tumour location, tumour stage and radiotherapy. This retrospective cohort study included 173 patients with rectal adenocarcinoma. CT colonography
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Phosphoproteomics revealed cellular signals immediately responding to disruption of cancer amino acid homeostasis induced by inhibition of l-type amino acid transporter 1 Cancer Metab. (IF 5.9) Pub Date : 2022-11-10 Okanishi, Hiroki, Ohgaki, Ryuichi, Xu, Minhui, Endou, Hitoshi, Kanai, Yoshikatsu
Cancer-upregulated l-type amino acid transporter 1 (LAT1; SLC7A5) supplies essential amino acids to cancer cells. LAT1 substrates are not only needed for cancer rapid growth, but involved in cellular signaling. LAT1 has been proposed as a potential target for cancer treatment—its inhibitor, JPH203, is currently in clinical trials and targets biliary tract cancer (BTC). Here, we revealed to what extent
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Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment Cancer Metab. (IF 5.9) Pub Date : 2022-10-26 Rosario, Spencer R., Smith, Randall J., Patnaik, Santosh K., Liu, Song, Barbi, Joseph, Yendamuri, Sai
Contrary to the “obesity paradox,” which arises from retrospective studies relying on body mass index to define obesity, epidemiologic evidence suggests central or visceral obesity is associated with a higher risk for the development of lung cancer. About 60% of individuals at high risk for developing lung cancer or those already with early-stage disease are either overweight or obese. Findings from
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Data-driven identification of plasma metabolite clusters and metabolites of interest for potential detection of early-stage non-small cell lung cancer cases versus cancer-free controls Cancer Metab. (IF 5.9) Pub Date : 2022-10-12 Kim, Julian O., Balshaw, Robert, Trevena, Connel, Banerji, Shantanu, Murphy, Leigh, Dawe, David, Tan, Lawrence, Srinathan, Sadeesh, Buduhan, Gordon, Kidane, Biniam, Qing, Gefei, Domaratzki, Michael, Aliani, Michel
Metabolomics is a potential means for biofluid-based lung cancer detection. We conducted a non-targeted, data-driven assessment of plasma from early-stage non-small cell lung cancer (ES-NSCLC) cases versus cancer-free controls (CFC) to explore and identify the classes of metabolites for further targeted metabolomics biomarker development. Plasma from 250 ES-NSCLC cases and 250 CFCs underwent ultra-high-performance
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Scaffold-mediated switching of lymphoma metabolism in culture Cancer Metab. (IF 5.9) Pub Date : 2022-10-12 Bhatt, Rachana, Ravi, Dashnamoorthy, Evens, Andrew M., Parekkadan, Biju
Diffuse large B cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL) and accounts for about a third of all NHL cases. A significant proportion (~40%) of treated DLBCL patients develop refractory or relapsed disease due to drug resistance which can be attributed to metabolomic and genetic variations amongst diverse DLBCL subtypes. An assay platform that reproduces metabolic patterns
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ACSL3 regulates lipid droplet biogenesis and ferroptosis sensitivity in clear cell renal cell carcinoma Cancer Metab. (IF 5.9) Pub Date : 2022-10-03 Klasson, Timothy D., LaGory, Edward L., Zhao, Hongjuan, Huynh, Star K., Papandreou, Ioanna, Moon, Eui Jung, Giaccia, Amato J.
Clear cell renal cell carcinoma (ccRCC), the predominant subtype of kidney cancer, possesses characteristic alterations to multiple metabolic pathways, including the accumulation of cytosolic lipid droplets. However, the pathways that drive lipid droplet accumulation in ccRCC cells and their importance to cancer biology remain poorly understood. We sought to identify the carbon sources necessary for
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Integrative analysis of plasma metabolomics and proteomics reveals the metabolic landscape of breast cancer Cancer Metab. (IF 5.9) Pub Date : 2022-08-17 An, Rui, Yu, Haitao, Wang, Yanzhong, Lu, Jie, Gao, Yuzhen, Xie, Xinyou, Zhang, Jun
Breast cancer (BC) is the most commonly diagnosed cancer. Currently, mammography and breast ultrasonography are the main clinical screening methods for BC. Our study aimed to reveal the specific metabolic profiles of BC patients and explore the specific metabolic signatures in human plasma for BC diagnosis. This study enrolled 216 participants, including BC patients, benign patients, and healthy controls
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Ketogenic diets slow melanoma growth in vivo regardless of tumor genetics and metabolic plasticity Cancer Metab. (IF 5.9) Pub Date : 2022-07-18 Weber, Daniela D., Aminzadeh-Gohari, Sepideh, Thapa, Maheshwor, Redtenbacher, Anna-Sophia, Catalano, Luca, Capelôa, Tânia, Vazeille, Thibaut, Emberger, Michael, Felder, Thomas K., Feichtinger, René G., Koelblinger, Peter, Dallmann, Guido, Sonveaux, Pierre, Lang, Roland, Kofler, Barbara
Growing evidence supports the use of low-carbohydrate/high-fat ketogenic diets as an adjunctive cancer therapy. However, it is unclear which genetic, metabolic, or immunological factors contribute to the beneficial effect of ketogenic diets. Therefore, we investigated the effect of ketogenic diets on the progression and metabolism of genetically and metabolically heterogeneous melanoma xenografts,
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13C tracer analysis suggests extensive recycling of endogenous CO2 in vivo Cancer Metab. (IF 5.9) Pub Date : 2022-07-07 Duan, Likun, Cooper, Daniel E., Scheidemantle, Grace, Locasale, Jason W., Kirsch, David G., Liu, Xiaojing
13C tracer analysis is increasingly used to monitor cellular metabolism in vivo and in intact cells, but data interpretation is still the key element to unveil the complexity of metabolic activities. The distinct 13C labeling patterns (e.g., M + 1 species in vivo but not in vitro) of metabolites from [U-13C]-glucose or [U-13C]-glutamine tracing in vivo and in vitro have been previously reported by
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Global metabolic alterations in colorectal cancer cells during irinotecan-induced DNA replication stress Cancer Metab. (IF 5.9) Pub Date : 2022-07-04 Marx, Christian, Sonnemann, Jürgen, Maddocks, Oliver D. K., Marx-Blümel, Lisa, Beyer, Mandy, Hoelzer, Doerte, Thierbach, René, Maletzki, Claudia, Linnebacher, Michael, Heinzel, Thorsten, Krämer, Oliver H.
Metabolic adaptations can allow cancer cells to survive DNA-damaging chemotherapy. This unmet clinical challenge is a potential vulnerability of cancer. Accordingly, there is an intense search for mechanisms that modulate cell metabolism during anti-tumor therapy. We set out to define how colorectal cancer CRC cells alter their metabolism upon DNA replication stress and whether this provides opportunities
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Metabolic flux analysis of 3D spheroids reveals significant differences in glucose metabolism from matched 2D cultures of colorectal cancer and pancreatic ductal adenocarcinoma cell lines Cancer Metab. (IF 5.9) Pub Date : 2022-05-16 Tidwell, Tia R., Røsland, Gro V., Tronstad, Karl Johan, Søreide, Kjetil, Hagland, Hanne R.
Most in vitro cancer cell experiments have been performed using 2D models. However, 3D spheroid cultures are increasingly favored for being more representative of in vivo tumor conditions. To overcome the translational challenges with 2D cell cultures, 3D systems better model more complex cell-to-cell contact and nutrient levels present in a tumor, improving our understanding of cancer complexity.
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An iron chelation-based combinatorial anticancer therapy comprising deferoxamine and a lactate excretion inhibitor inhibits the proliferation of cancer cells Cancer Metab. (IF 5.9) Pub Date : 2022-05-12 Fujisawa, Koichi, Takami, Taro, Matsumoto, Toshihiko, Yamamoto, Naoki, Yamasaki, Takahiro, Sakaida, Isao
Although iron chelation has garnered attention as a novel therapeutic strategy for cancer, higher levels of efficacy need to be achieved. In the present study, we examined the combinatorial effect of deferoxamine (DFO), an iron chelator, and α-cyano-4-hydroxy cinnamate (CHC), a suppressor of lactate excretion, on the proliferation of cancer cell lines. We established a deferoxamine (DFO)-resistant
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Identification of novel lipid biomarkers in xmrk- and Myc-induced models of hepatocellular carcinoma in zebrafish Cancer Metab. (IF 5.9) Pub Date : 2022-04-04 Monroe, Jerry D., Fraher, Daniel, Huang, Xiaoqian, Mellett, Natalie A., Meikle, Peter J., Sinclair, Andrew J., Lirette, Seth T., Maihle, Nita J., Gong, Zhiyuan, Gibert, Yann
Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and is accompanied by complex dysregulation of lipids. Increasing evidence suggests that particular lipid species are associated with HCC progression. Here, we aimed to identify lipid biomarkers of HCC associated with the induction of two oncogenes, xmrk, a zebrafish homolog of the human epidermal growth factor receptor (EGFR),
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Combined inhibition of HMGCoA reductase and mitochondrial complex I induces tumor regression of BRAF inhibitor-resistant melanomas Cancer Metab. (IF 5.9) Pub Date : 2022-02-22 de Groot, Evelyn, Varghese, Sruthy, Tan, Lin, Knighton, Barbara, Sobieski, Mary, Nguyen, Nghi, Park, Yong Sung, Powell, Reid, Lorenzi, Philip L., Zheng, Bin, Stephan, Clifford, Gopal, Y. N. Vashisht
Primary and posttreatment resistance to BRAFV600 mutation–targeting inhibitors leads to disease relapse in a majority of melanoma patients. In many instances, this resistance is promoted by upregulation of mitochondrial oxidative phosphorylation (OxPhos) in melanoma cells. We recently showed that a novel electron transport chain (ETC) complex I inhibitor, IACS-010759 (IACS), abolished OxPhos and significantly
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Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics Cancer Metab. (IF 5.9) Pub Date : 2022-02-21 Zhang, Anni M. Y., Chu, Ken H., Daly, Brian F., Ruiter, Titine, Dou, Yan, Yang, Jenny C. C., de Winter, Twan J. J., Chhuor, Justin, Wang, Su, Flibotte, Stephane, Zhao, Yiwei Bernie, Hu, Xiaoke, Li, Hong, Rideout, Elizabeth J., Schaeffer, David F., Johnson, James D., Kopp, Janel L.
Hyperinsulinemia is independently associated with increased risk and mortality of pancreatic cancer. We recently reported that genetically reduced insulin production resulted in ~ 50% suppression of pancreatic intraepithelial neoplasia (PanIN) precancerous lesions in mice. However, only female mice remained normoglycemic, and only the gene dosage of the rodent-specific Ins1 alleles was tested in our
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Glucagon signaling via supraphysiologic GCGR can reduce cell viability without stimulating gluconeogenic gene expression in liver cancer cells Cancer Metab. (IF 5.9) Pub Date : 2022-02-05 Godfrey, Jason, Riscal, Romain, Skuli, Nicolas, Simon, M. Celeste
Deregulated glucose metabolism is a critical component of cancer growth and survival, clinically evident via FDG-PET imaging of enhanced glucose uptake in tumor nodules. Tumor cells utilize glucose in a variety of interconnected biochemical pathways to generate energy, anabolic precursors, and other metabolites necessary for growth. Glucagon-stimulated gluconeogenesis opposes glycolysis, potentially
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Novel humanized monoclonal antibodies for targeting hypoxic human tumors via two distinct extracellular domains of carbonic anhydrase IX Cancer Metab. (IF 5.9) Pub Date : 2022-02-02 Zatovicova, Miriam, Kajanova, Ivana, Barathova, Monika, Takacova, Martina, Labudova, Martina, Csaderova, Lucia, Jelenska, Lenka, Svastova, Eliska, Pastorekova, Silvia, Harris, Adrian L., Pastorek, Jaromir
Hypoxia in the tumor microenvironment (TME) is often the main factor in the cancer progression. Moreover, low levels of oxygen in tumor tissue may signal that the first- or second-line therapy will not be successful. This knowledge triggers the inevitable search for different kinds of treatment that will successfully cure aggressive tumors. Due to its exclusive expression on cancer cells, carbonic
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MicroRNA-377-3p inhibits hepatocellular carcinoma growth and metastasis through negative regulation of CPT1C-mediated fatty acid oxidation Cancer Metab. (IF 5.9) Pub Date : 2022-01-20 Zhang, Ting, Zhang, Yanan, Liu, Jie, Ma, Yan, Ye, Qinong, Yan, Xinlong, Ding, Lihua
Altered lipid metabolism is closely related to the occurrence and development of hepatocellular carcinoma (HCC). Carnitine palmitoyltransferase 1C (CPT1C) is a member of CPT1 family and plays a key role in cancer development and progression. However, how microRNAs (miRNAs) regulate CPT1C-mediated fatty acid transport and oxidation remains to be elucidated. Oil Red O staining, mitochondrial, and lipid
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Prostate cancer cell proliferation is influenced by LDL-cholesterol availability and cholesteryl ester turnover Cancer Metab. (IF 5.9) Pub Date : 2022-01-15 Raftopulos, Nikki L., Washaya, Tinashe C., Niederprüm, Andreas, Egert, Antonia, Hakeem-Sanni, Mariam F., Varney, Bianca, Aishah, Atqiya, Georgieva, Mariya L., Olsson, Ellinor, dos Santos, Diandra Z., Nassar, Zeyad D., Cochran, Blake J., Nagarajan, Shilpa R., Kakani, Meghna S., Hastings, Jordan F., Croucher, David R., Rye, Kerry-Anne, Butler, Lisa M., Grewal, Thomas, Hoy, Andrew J.
Prostate cancer growth is driven by androgen receptor signaling, and advanced disease is initially treatable by depleting circulating androgens. However, prostate cancer cells inevitably adapt, resulting in disease relapse with incurable castrate-resistant prostate cancer. Androgen deprivation therapy has many side effects, including hypercholesterolemia, and more aggressive and castrate-resistant
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Loss of hexokinase 1 sensitizes ovarian cancer to high-dose metformin Cancer Metab. (IF 5.9) Pub Date : 2021-12-11 Šimčíková, Daniela, Gardáš, Dominik, Hložková, Kateřina, Hruda, Martin, Žáček, Petr, Rob, Lukáš, Heneberg, Petr
Hexokinases (HKs) are well-studied enzymes catalyzing the first step of glycolysis. However, non-canonical regulatory roles of HKs are still incompletely understood. Here, we hypothesized that HKs comprise one of the missing links between high-dose metformin and the inhibition of the respiratory chain in cancer. We tested the isoenzyme-specific regulatory roles of HKs in ovarian cancer cells by examining