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  • ARNT deficiency represses pyruvate dehydrogenase kinase 1 to trigger ROS production and melanoma metastasis
    Oncogenesis (IF 6.119) Pub Date : 2021-01-14
    Chi-Ruei Huang; Ting-Wei Chang; Chung-Ta Lee; Chih-Jie Shen; Wen-Chang Chang; Ben-Kuen Chen

    The metabolic changes in melanoma cells that are required for tumor metastasis have not been fully elucidated. In this study, we show that the increase in glucose uptake and mitochondrial oxidative phosphorylation confers metastatic ability as a result of aryl hydrocarbon receptor nuclear translocator (ARNT) deficiency. In clinical tissue specimens, increased ARNT, pyruvate dehydrogenase kinase 1 (PDK1)

  • Prolactin receptor-driven combined luminal and epithelial differentiation in breast cancer restricts plasticity, stemness, tumorigenesis and metastasis
    Oncogenesis (IF 6.119) Pub Date : 2021-01-14
    Anwar Shams; Najat Binothman; Julien Boudreault; Ni Wang; Fuad Shams; Dana Hamam; Jun Tian; Alaa Moamer; Meiou Dai; Jean-Jacques Lebrun; Suhad Ali

    Dedifferentiation increased cellular plasticity and stemness are established derivers of tumor heterogeneity, metastasis and therapeutic failure resulting in incurable cancers. Therefore, it is essential to decipher pro/forward-differentiation mechanisms in cancer that may serve as therapeutic targets. We found that interfering with expression of the receptor for the lactogenic hormone prolactin (PRLR)

  • Metformin exhibits antiproliferation activity in breast cancer via miR-483-3p/METTL3/m 6 A/p21 pathway
    Oncogenesis (IF 6.119) Pub Date : 2021-01-05
    Lin Cheng; Xu Zhang; Yu-Zhou Huang; Yu-Lan Zhu; Ling-Yun Xu; Zhi Li; Xin-Yuan Dai; Liang Shi; Xu-Jie Zhou; Ji-Fu Wei; Qiang Ding

    Evidence suggests that metformin might be a potential candidate for breast cancer treatment. Yet, its relevant molecular mechanisms remain to be fully investigated. We found that metformin could suppress the N6-methyladenosine (m6A) level in breast cancer cells significantly. The latter has an essential role in breast cancer progression and is newly considered as a therapeutic target. In this study

  • PBK phosphorylates MSL1 to elicit epigenetic modulation of CD276 in nasopharyngeal carcinoma
    Oncogenesis (IF 6.119) Pub Date : 2021-01-05
    Meng-Yao Wang; Bin Qi; Fang Wang; Zhi-Rui Lin; Ming-Yi Li; Wen-Jing Yin; Yan-Yi Zhu; Lu He; Yi Yu; Fang Yang; Jin-Quan Liu; Dong-Ping Chen

    CD276 (also known as B7–H3, an immune checkpoint molecule) is aberrantly overexpressed in many cancers. However, the upregulation mechanism and in particular, whether oncogenic signaling has a role, is unclear. Here we demonstrate that a pro-oncogenic kinase PBK, the expression of which is associated with immune infiltration in nasopharyngeal carcinoma (NPC), stimulates the expression of CD276 epigenetically

  • Feedback activation of STAT3 limits the response to PI3K/AKT/mTOR inhibitors in PTEN-deficient cancer cells
    Oncogenesis (IF 6.119) Pub Date : 2021-01-05
    Jian Wang; Xiaoye Lv; Xiutian Guo; Yanbo Dong; Peipei Peng; Fang Huang; Peng Wang; Haoqian Zhang; Jianguang Zhou; Youliang Wang; Bo Wei; Zeng-Fu Shang; Shanhu Li

    The PI3K/AKT/mTOR signaling pathway is constitutively active in PTEN-deficient cancer cells, and its targeted inhibition has significant anti-tumor effects. However, the efficacy of targeted therapies is often limited due to drug resistance. The relevant signaling pathways in PTEN-deficient cancer cells treated with the PI3K/mTOR inhibitor BEZ235 were screened using a phosphokinase array, and further

  • FAM83B inhibits ovarian cancer cisplatin resistance through inhibiting Wnt pathway
    Oncogenesis (IF 6.119) Pub Date : 2021-01-09
    Shanyang He; Wei Wang; Zhiyong Wan; Hongwei Shen; Yunhe Zhao; Zeshan You; Jun Liu; Liwen Zhu

    Cisplatin resistance is frequently occurred in ovarian cancer therapy, understanding its regulatory mechanisms is critical for developing novel treatment methods and drugs. Here, we found ovarian cancer patients with low FAM83B levels had shorter survival time, tissues with cisplatin resistance also had low FAM83B levels, suggesting FAM83B might inhibit cisplatin resistance. FAM83B overexpression inhibits

  • A novel role of MNT as a negative regulator of REL and the NF-κB pathway
    Oncogenesis (IF 6.119) Pub Date : 2021-01-08
    Judit Liaño-Pons; M. Carmen Lafita-Navarro; Lorena García-Gaipo; Carlota Colomer; Javier Rodríguez; Alex von Kriegsheim; Peter J. Hurlin; Fabiana Ourique; M. Dolores Delgado; Anna Bigas; M. Lluis Espinosa; Javier León

    MNT, a transcription factor of the MXD family, is an important modulator of the oncoprotein MYC. Both MNT and MYC are basic-helix–loop–helix proteins that heterodimerize with MAX in a mutually exclusive manner, and bind to E-boxes within regulatory regions of their target genes. While MYC generally activates transcription, MNT represses it. However, the molecular interactions involving MNT as a transcriptional

  • Understanding the common mechanisms of heart and skeletal muscle wasting in cancer cachexia
    Oncogenesis (IF 6.119) Pub Date : 2021-01-08
    Valentina Rausch; Valentina Sala; Fabio Penna; Paolo Ettore Porporato; Alessandra Ghigo

    Cachexia is a severe complication of cancer that adversely affects the course of the disease, with currently no effective treatments. It is characterized by a progressive atrophy of skeletal muscle and adipose tissue, resulting in weight loss, a reduced quality of life, and a shortened life expectancy. Although the cachectic condition primarily affects the skeletal muscle, a tissue that accounts for

  • Diethyldithiocarbamate-copper complex (CuET) inhibits colorectal cancer progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis-mediated aerobic glycolysis pathway
    Oncogenesis (IF 6.119) Pub Date : 2021-01-08
    Xin Huang; Yichao Hou; Xiaoling Weng; Wenjing Pang; Lidan Hou; Yu Liang; Yu Wang; Leilei Du; Tianqi Wu; Mengfei Yao; Jianhua Wang; Xiangjun Meng

    Exploring novel anticancer drugs to optimize the efficacy may provide a benefit for the treatment of colorectal cancer (CRC). Disulfiram (DSF), as an antialcoholism drug, is metabolized into diethyldithiocarbamate-copper complex (CuET) in vivo, which has been reported to exert the anticancer effects on various tumors in preclinical studies. However, little is known about whether CuET plays an anti-cancer

  • Emerging role of SWI/SNF complex deficiency as a target of immune checkpoint blockade in human cancers
    Oncogenesis (IF 6.119) Pub Date : 2021-01-08
    Min Zhou; Jianlong Yuan; Yaqi Deng; Xianqun Fan; Jianfeng Shen

    Mammalian SWI/SNF complex is a key chromatin remodeler that reshapes nucleosomes and regulates DNA accessibility. Mutations in SWI/SNF subunits are found in a broad spectrum of human cancers; however, the mechanisms of how these aberrations of SWI/SNF complex would impact tumorigenesis and cancer therapeutics remain to be elucidated. Studies have demonstrated that immune checkpoint blockade (ICB) therapy

  • YAP/TAZ inhibition reduces metastatic potential of Ewing sarcoma cells
    Oncogenesis (IF 6.119) Pub Date : 2021-01-08
    Lisa Bierbaumer; Anna M. Katschnig; Branka Radic-Sarikas; Maximilian O. Kauer; Jeffrey A. Petro; Sandra Högler; Elisabeth Gurnhofer; Gloria Pedot; Beat W. Schäfer; Raphaela Schwentner; Karin Mühlbacher; Florian Kromp; Dave N. T. Aryee; Lukas Kenner; Aykut Uren; Heinrich Kovar

    Ewing sarcoma (EwS) is a highly metastatic bone cancer characterized by the ETS fusion oncoprotein EWS-FLI1. EwS cells are phenotypically highly plastic and switch between functionally distinct cell states dependent on EWS-FLI1 fluctuations. Whereas EWS-FLI1high cells proliferate, EWS-FLI1low cells are migratory and invasive. Recently, we reported activation of MRTFB and TEAD, effectors of RhoA and

  • OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression
    Oncogenesis (IF 6.119) Pub Date : 2020-12-11
    Mirco Masi; Enrico Garattini; Marco Bolis; Daniele Di Marino; Luisa Maraccani; Elena Morelli; Ambra A. Grolla; Francesca Fagiani; Emanuela Corsini; Cristina Travelli; Stefano Govoni; Marco Racchi; Erica Buoso

    Recent data indicate that receptor for activated C kinase 1 (RACK1) is a putative prognostic marker and drug target in breast cancer (BC). High RACK1 expression is negatively associated with overall survival, as it seems to promote BC progression. In tumors, RACK1 expression is controlled by a complex balance between glucocorticoids and androgens. Given the fact that androgens and androgenic derivatives

  • The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate
    Oncogenesis (IF 6.119) Pub Date : 2020-12-07
    Jia-Lin Shiu; Cheng-Kuei Wu; Song-Bin Chang; Yan-Jhih Sun; Yen-Ju Chen; Chien-Chen Lai; Wen-Tai Chiu; Wen-Tsan Chang; Kyungjae Myung; Wen-Pin Su; Hungjiun Liaw

    Human HLTF participates in the lesion-bypass mechanism through the fork reversal structure, known as template switching of post-replication repair. However, the mechanism by which HLTF promotes the replication progression and fork stability of damaged forks remains unclear. Here, we identify a novel protein–protein interaction between HLTF and PARP1. The depletion of HLTF and PARP1 increases chromosome

  • Non-metabolic role of UCK2 links EGFR-AKT pathway activation to metastasis enhancement in hepatocellular carcinoma
    Oncogenesis (IF 6.119) Pub Date : 2020-12-04
    Jie Cai; Xuehua Sun; Han Guo; Xiaoye Qu; Hongting Huang; Chang Yu; Hailong Wu; Yueqiu Gao; Xiaoni Kong; Qiang Xia

    Up-regulation of Uridine-cytidine kinase 2 (UCK2), a rate-limiting enzyme of the pyrimidine salvage pathway, has been suggested in HCC, but the detailed molecular mechanisms and therapic role of UCK2 remain elusive. Bioinformatic analyses revealed that UCK2 might be a key up-regulated metabolic gene in HCCs. The expressional pattern and prognostic value of UCK2 were further examined in a large number

  • Functional screening identifies aryl hydrocarbon receptor as suppressor of lung cancer metastasis
    Oncogenesis (IF 6.119) Pub Date : 2020-11-19
    Silke Nothdurft; Clotilde Thumser-Henner; Frank Breitenbücher; Ross A. Okimoto; Madeleine Dorsch; Christiane A. Opitz; Ahmed Sadik; Charlotte Esser; Michael Hölzel; Saurabh Asthana; Jan Forster; Daniela Beisser; Sophie Kalmbach; Barbara M. Grüner; Trever G. Bivona; Alexander Schramm; Martin Schuler

    Lung cancer mortality largely results from metastasis. Despite curative surgery many patients with early-stage non-small cell lung cancer ultimately succumb to metastatic relapse. Current risk reduction strategies based on cytotoxic chemotherapy and radiation have only modest activity. Against this background, we functionally screened for novel metastasis modulators using a barcoded shRNA library and

  • MiR-22 , regulated by MeCP2, suppresses gastric cancer cell proliferation by inducing a deficiency in endogenous S-adenosylmethionine
    Oncogenesis (IF 6.119) Pub Date : 2020-11-10
    Dongdong Tong; Jing Zhang; Xiaofei Wang; Qian Li; Liying Liu; Axin Lu; Bo Guo; Juan Yang; Lei Ni; Hao Qin; Lingyu Zhao; Chen Huang

    This study investigated the effect of methyl-CpG-binding protein 2 (MeCP2) on miRNA transcription. Our results of miRNA chip assay and ChIP-seq showed that MeCP2 inhibited the expressions of numerous miRNAs by binding to their upstream elements, including not only the promoter but also the distal enhancer. Among the affected miRNAs, miR-22 was identified to remarkably suppress gastric cancer (GC) cell

  • EZH2 facilitates BMI1-dependent hepatocarcinogenesis through epigenetically silencing microRNA-200c
    Oncogenesis (IF 6.119) Pub Date : 2020-11-09
    Leibo Xu; Junlong Lin; Wanyu Deng; Weixin Luo; Yipei Huang; Chao-Qun Liu; Fa-Peng Zhang; Yu-Fei Qin; Ping-Pui Wong; Chao Liu

    EZH2, a histone methyltransferase, has been shown to involve in cancer development and progression via epigenetic regulation of tumor suppressor microRNAs, whereas BMI1, a driver of hepatocellular carcinoma (HCC), is a downstream target of these microRNAs. However, it remains unclear whether EZH2 can epigenetically regulate microRNA expression to modulate BMI1-dependent hepatocarcinogenesis. Here,

  • Triptolide targets super-enhancer networks in pancreatic cancer cells and cancer-associated fibroblasts
    Oncogenesis (IF 6.119) Pub Date : 2020-11-09
    Pawan Noel; Shaimaa Hussein; Serina Ng; Corina E. Antal; Wei Lin; Emily Rodela; Priscilla Delgado; Sanna Naveed; Michael Downes; Yin Lin; Ronald M. Evans; Daniel D. Von Hoff; Haiyong Han

    The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is highly heterogeneous, fibrotic, and hypovascular, marked by extensive desmoplasia and maintained by the tumor cells, cancer-associated fibroblasts (CAFs) and other stromal cells. There is an urgent need to identify and develop treatment strategies that not only target the tumor cells but can also modulate the stromal cells. A

  • The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer
    Oncogenesis (IF 6.119) Pub Date : 2020-10-31
    Le Shi; Dongyue Du; Yunhua Peng; Jiankang Liu; Jiangang Long

    Cullin (CUL) proteins have critical roles in development and cancer, however few studies on CUL7 have been reported due to its characteristic molecular structure. CUL7 forms a complex with the ROC1 ring finger protein, and only two F-box proteins Fbxw8 and Fbxw11 have been shown to bind to CUL7. Interestingly, CUL7 can interact with its substrates by forming a novel complex that is independent of these

  • Nuclear FOXP3 inhibits tumor growth and induced apoptosis in hepatocellular carcinoma by targeting c-Myc
    Oncogenesis (IF 6.119) Pub Date : 2020-10-28
    Zhongqin Gong; Hao Jia; Jianqing Yu; Yi Liu; Jianwei Ren; Shengli Yang; Baoguang Hu; Liping Liu; Paul B. S. Lai; George Gong Chen

    The status of FOXP3 and its isoforms in hepatocellular carcinoma (HCC) is unclear. We aimed to investigate the expression and function of FOXP3 and its isoforms in HCC. The study was performed on 84 HCC patients, HCC cell lines and a mouse tumor model. The levels of FOXP3 and its isoforms were determined by nested PCR, quantitative real-time PCR and immunohistochemistry (IHC) staining. The correlation

  • Breast tumor cells promotes the horizontal propagation of EMT, stemness, and metastasis by transferring the MAP17 protein between subsets of neoplastic cells
    Oncogenesis (IF 6.119) Pub Date : 2020-10-26
    José Manuel García-Heredia; Daniel Otero-Albiol; Marco Pérez; Elena Pérez-Castejón; Sandra Muñoz-Galván; Amancio Carnero

    MAP17 (PDZK1IP1) is a small protein regulating inflammation and tumor progression, upregulated in a broad range of carcinomas. MAP17 levels increase during tumor progression in a large percentage of advanced tumors. In the present work, we explored the role of this protein shaping tumor evolution. Here we show that in breast cancer, cells increased MAP17 levels in tumors by demethylation induced multiple

  • microRNA-199a-3p inhibits hepatic apoptosis and hepatocarcinogenesis by targeting PDCD4
    Oncogenesis (IF 6.119) Pub Date : 2020-10-24
    Zhenyang Li; Ye Zhou; Liyuan Zhang; Kaiwei Jia; Suyuan Wang; Mu Wang; Nan Li; Yizhi Yu; Xuetao Cao; Jin Hou

    Hepatic apoptosis and the initiated liver inflammation play the initial roles in inflammation-induced hepatocarcinogenesis. Molecular mechanisms underlying the regulation of hepatocyte apoptosis and their roles in hepatocarcinogenesis have attracted much attention. A set of microRNAs (miRNAs) have been determined to be dysregulated in hepatocellular carcinoma (HCC) and participated in cancer progression

  • Antileukemic activity of the VPS34-IN1 inhibitor in acute myeloid leukemia
    Oncogenesis (IF 6.119) Pub Date : 2020-10-22
    Godelieve Meunier; Rudy Birsen; Clarisse Cazelles; Maya Belhadj; Lilia Cantero-Aguilar; Olivier Kosmider; Michaela Fontenay; Nabih Azar; Patrick Mayeux; Nicolas Chapuis; Jerôme Tamburini; Didier Bouscary

    Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. Vacuolar protein sorting 34 (VPS34) is a member of the phosphatidylinositol-3-kinase lipid kinase family that controls the canonical autophagy pathway and vesicular trafficking. Using a recently developed specific inhibitor (VPS34-IN1), we found that VPS34 inhibition induces apoptosis in AML cells but not in normal CD34+ hematopoietic

  • Notch3 contributes to T-cell leukemia growth via regulation of the unfolded protein response
    Oncogenesis (IF 6.119) Pub Date : 2020-10-18
    Maria Valeria Giuli; Giulia Diluvio; Eugenia Giuliani; Giulia Franciosa; Laura Di Magno; Maria Gemma Pignataro; Luca Tottone; Carmine Nicoletti; Zein Mersini Besharat; Giovanna Peruzzi; Maria Pelullo; Rocco Palermo; Gianluca Canettieri; Claudio Talora; Giulia d’Amati; Diana Bellavia; Isabella Screpanti; Saula Checquolo

    Unfolded protein response (UPR) is a conserved adaptive response that tries to restore protein homeostasis after endoplasmic reticulum (ER) stress. Recent studies highlighted the role of UPR in acute leukemias and UPR targeting has been suggested as a therapeutic approach. Aberrant Notch signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL), as downregulation of Notch activity

  • Aberrant super-enhancer landscape reveals core transcriptional regulatory circuitry in lung adenocarcinoma
    Oncogenesis (IF 6.119) Pub Date : 2020-10-17
    Te Zhang; Xuming Song; Zeyu Zhang; Qixing Mao; Wenjie Xia; Lin Xu; Feng Jiang; Gaochao Dong

    Lung adenocarcinoma (LUAD) relies on dysregulated gene expression to sustain its infinite growth and progression. Emerging evidence indicates that aberrant transcriptional program results from core transcriptional regulatory circuitry (CRC) which is driven by super-enhancers (SEs). In this study, by integrating profiles of H3K27Ac chromatin immunoprecipitation sequencing (ChIP-seq) from normal adult

  • Inhibition of Chk1 by miR-320c increases oxaliplatin responsiveness in triple-negative breast cancer
    Oncogenesis (IF 6.119) Pub Date : 2020-10-11
    Sera Lim; Yesol Kim; Soo-Been Lee; Hyeok-Gu Kang; Da-Hyun Kim; Jee Won Park; Daeun Chung; Hyunkyung Kong; Kyung Hyun Yoo; Yonghwan Kim; Wonshik Han; Kyung-Hee Chun; Jong Hoon Park

    Checkpoint kinase 1 (Chk1) expression is enhanced in most cancers owing to oncogenic activation and constant replicative stress. Chk1 inactivation is a promising cancer therapy, as its inactivation leads to genomic instability, chromosomal catastrophe, and cancer cell death. Herein, we observed that miR-320c, downregulated in triple-negative breast cancer (TNBC) patients, can target Chk1. In addition

  • TAp63α targeting of Lgr5 mediates colorectal cancer stem cell properties and sulforaphane inhibition
    Oncogenesis (IF 6.119) Pub Date : 2020-10-10
    Yue Chen; Meng-huan Wang; Jian-yun Zhu; Chun-feng Xie; Xiao-ting Li; Jie-shu Wu; Shan-shan Geng; Hong-yu Han; Cai-yun Zhong

    Cancer stem cells (CSCs) have an established role in cancer progression and therapeutic resistance. The p63 proteins are important transcription factors which belong to the p53 family, but their function and mechanism in CSCs remain elusive. Here, we investigated the role of TAp63α in colorectal CSCs and the effects of sulforaphane on TAp63α. We found that TAp63α was upregulated in spheres with stem

  • Targeting IL-3Rα on tumor-derived endothelial cells blunts metastatic spread of triple-negative breast cancer via extracellular vesicle reprogramming
    Oncogenesis (IF 6.119) Pub Date : 2020-10-10
    Tatiana Lopatina; Cristina Grange; Claudia Cavallari; Victor Navarro-Tableros; Giusy Lombardo; Arturo Rosso; Massimo Cedrino; Margherita Alba Carlotta Pomatto; Malvina Koni; Francesca Veneziano; Isabella Castellano; Giovanni Camussi; Maria Felice Brizzi

    The lack of approved targeted therapies highlights the need for new treatments for triple-negative breast cancer (TNBC) patients. Interleukin-3 (IL-3) acts as an autocrine factor for tumor–endothelial cells (TEC), and exerts pro-angiogenic paracrine action via extracellular vesicles (EVs). IL-3Rα blockade on TEC changes TEC-EV (anti-IL-3R-EV) microRNA (miR) content and promotes the regression of established

  • Overexpression of Cyclin E1 or Cdc25A leads to replication stress, mitotic aberrancies, and increased sensitivity to replication checkpoint inhibitors
    Oncogenesis (IF 6.119) Pub Date : 2020-10-07
    Yannick P. Kok; Sergi Guerrero Llobet; Pepijn M. Schoonen; Marieke Everts; Arkajyoti Bhattacharya; Rudolf S. N. Fehrmann; Nathalie van den Tempel; Marcel A. T. M. van Vugt

    Oncogene-induced replication stress, for instance as a result of Cyclin E1 overexpression, causes genomic instability and has been linked to tumorigenesis. To survive high levels of replication stress, tumors depend on pathways to deal with these DNA lesions, which represent a therapeutically actionable vulnerability. We aimed to uncover the consequences of Cyclin E1 or Cdc25A overexpression on replication

  • WAVE3 phosphorylation regulates the interplay between PI3K, TGF-β, and EGF signaling pathways in breast cancer
    Oncogenesis (IF 6.119) Pub Date : 2020-10-05
    Wei Wang; Urna Kansakar; Vesna Markovic; Bingcheng Wang; Khalid Sossey-Alaoui

    Both TGF-β and the PI3K-AKT signaling pathways are known activators of various intracellular pathways that regulate critical cellular functions, including cancer cell survival and proliferation. The interplay between these two oncogenic pathways plays a major role in promoting the initiation, growth, and progression of tumors, including breast cancers. The molecular underpinning of the inter-relationship

  • Epigenetic activation of the small GTPase TCL contributes to colorectal cancer cell migration and invasion
    Oncogenesis (IF 6.119) Pub Date : 2020-09-30
    Baoyu Chen; Zhiwen Fan; Lina Sun; Junliang Chen; Yifei Feng; Xiangshan Fan; Yong Xu

    TC10-like (TCL) is a small GTPase that has been implicated in carcinogenesis. Elevated TCL expression has been observed in many different types of cancers although the underlying epigenetic mechanism is poorly understood. Here we report that TCL up-regulation was associated with high malignancy in both human colorectal cancer biopsy specimens and in cultured colorectal cancer cells. Hypoxia, a pro-metastatic

  • Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation
    Oncogenesis (IF 6.119) Pub Date : 2020-09-28
    Chao Wang; Zhen Chen; Litong Nie; Mengfan Tang; Xu Feng; Dan Su; Huimin Zhang; Yun Xiong; Jeong-Min Park; Junjie Chen

    The ERK1/2 pathway is one of the most commonly dysregulated pathways in human cancers and controls many vital cellular processes. Although many ERK1/2 kinase substrates have been identified, the diversity of ERK1/2 mediated processes suggests the existence of additional targets. Here, we identified Deoxyhypusine synthase (DHPS), an essential hypusination enzyme regulating protein translation, as a

  • A novel β2-AR/YB-1/β-catenin axis mediates chronic stress-associated metastasis in hepatocellular carcinoma
    Oncogenesis (IF 6.119) Pub Date : 2020-09-24
    Jinxia Liu; Lishuai Qu; Chunhua Wan; Mingbing Xiao; Wenkai Ni; Feng Jiang; Yihui Fan; Cuihua Lu; Runzhou Ni

    β-Adrenergic receptor (β-AR) signalling is strongly associated with tumour progression by the coupling of β-ARs with either a G protein or β-arrestin; however, the related mechanism underlying hepatocellular carcinoma (HCC) metastasis is not clear. Here, we reveal that the transcription factor Y-box binding protein 1 (YB-1) interacts with β2-adrenergic receptor (β2-AR) following stimulation with the

  • The membrane-associated form of cyclin D1 enhances cellular invasion.
    Oncogenesis (IF 6.119) Pub Date : 2020-09-18
    Ke Chen,Xuanmao Jiao,Anthony Ashton,Agnese Di Rocco,Timothy G Pestell,Yunguang Sun,Jun Zhao,Mathew C Casimiro,Zhiping Li,Michael P Lisanti,Peter A McCue,Duanwen Shen,Samuel Achilefu,Hallgeir Rui,Richard G Pestell

    The essential G1-cyclin, CCND1, is a collaborative nuclear oncogene that is frequently overexpressed in cancer. D-type cyclins bind and activate CDK4 and CDK6 thereby contributing to G1–S cell-cycle progression. In addition to the nucleus, herein cyclin D1 was also located in the cytoplasmic membrane. In contrast with the nuclear-localized form of cyclin D1 (cyclin D1NL), the cytoplasmic membrane-localized

  • Tumor-derived HMGB1 induces CD62Ldim neutrophil polarization and promotes lung metastasis in triple-negative breast cancer.
    Oncogenesis (IF 6.119) Pub Date : 2020-09-17
    Zhen Wang,Chenghui Yang,Lili Li,Xiaoyan Jin,Zhigang Zhang,Haiyan Zheng,Jun Pan,Liyun Shi,Zhou Jiang,Ke Su,Baizhou Li,Xuan Shao,Fuming Qiu,Jun Yan,Jian Huang

    Triple-negative breast cancer (TNBC) is highly aggressive, difficult to treat and commonly develops visceral metastasis, including lung metastasis. We observed that High mobility group box 1 protein (HMGB1) was highly expressed in human TNBC and positively correlated with cancer metastasis. The hypoxic tumor environment is known to regulate HMGB1 secretion, but an understanding of the underlying mechanism

  • Hypoxia induces an endometrial cancer stem-like cell phenotype via HIF-dependent demethylation of SOX2 mRNA.
    Oncogenesis (IF 6.119) Pub Date : 2020-09-11
    Guofang Chen,Binya Liu,Shasha Yin,Shuangdi Li,Yu'e Guo,Mengfei Wang,Kai Wang,Xiaoping Wan

    Endometrial cancer stem cells (ECSCs) are stem-like cells endowed with self-renewal and differentiation abilities, and these cells are essential for cancer progression in endometrial cancer (EC). As hallmarks of the tumour microenvironment (TME), hypoxia and hypoxia-inducing factors (HIFs) give rise to the dysregulation of tumour stemness genes, such as SOX2. Against this backdrop, we investigated

  • Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) with OT-82 induces DNA damage, cell death, and suppression of tumor growth in preclinical models of Ewing sarcoma.
    Oncogenesis (IF 6.119) Pub Date : 2020-09-10
    Anna E Gibson,Choh Yeung,Sameer H Issaq,Victor J Collins,Michael Gouzoulis,Yiping Zhang,Jiuping Ji,Arnulfo Mendoza,Christine M Heske

    NAMPT mediates the rate-limiting step of the NAD salvage pathway, which maintains cellular bioenergetics and provides a necessary substrate for functions essential to rapidly proliferating cancer cells. In this study, we evaluated the efficacy and mechanisms of action of OT-82, a novel, high-potency NAMPT inhibitor with a favorable toxicity profile, in preclinical models of Ewing sarcoma (EWS), an

  • Altering MYC phosphorylation in the epidermis increases the stem cell population and contributes to the development, progression, and metastasis of squamous cell carcinoma.
    Oncogenesis (IF 6.119) Pub Date : 2020-09-07
    Xiaoyan Wang,Ellen M Langer,Colin J Daniel,Mahnaz Janghorban,Vivian Wu,Xiao-Jing Wang,Rosalie C Sears

    cMYC (MYC) is a potent oncoprotein that is subject to post-translational modifications that affect its stability and activity. Here, we show that Serine 62 phosphorylation, which increases MYC stability and oncogenic activity, is elevated while Threonine 58 phosphorylation, which targets MYC for degradation, is decreased in squamous cell carcinoma (SCC). The oncogenic role of MYC in the development

  • Squalene synthase promotes the invasion of lung cancer cells via the osteopontin/ERK pathway.
    Oncogenesis (IF 6.119) Pub Date : 2020-08-29
    Yi-Fang Yang,Yu-Chan Chang,Yi-Hua Jan,Chih-Jen Yang,Ming-Shyan Huang,Michael Hsiao

    Cholesterol is the major component of lipid rafts. Squalene synthase (SQS) is a cholesterol biosynthase that functions in cholesterol biosynthesis, modulates the formation of lipids rafts and promotes lung cancer metastasis. In this study, we investigated the lipid raft-associated pathway of SQS in lung cancer. Gene expression microarray data revealed the upregulation of secreted phosphoprotein 1 (SPP1;

  • LIMK2 promotes the metastatic progression of triple-negative breast cancer by activating SRPK1.
    Oncogenesis (IF 6.119) Pub Date : 2020-08-28
    Parmanand Malvi,Radoslav Janostiak,Suresh Chava,Padmini Manrai,Esther Yoon,Kamaljeet Singh,Malini Harigopal,Romi Gupta,Narendra Wajapeyee

    Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype and due to the lack of hormone receptors and HER2 expression, TNBC has limited therapeutic options with chemotherapy being the primary choice for systemic therapy. LIM Domain Kinase 2 (LIMK2) is a serine/threonine kinase that plays an important role in the regulation of actin filament dynamics. Here, we show that LIM

  • Methyl-CpG-binding protein 2 drives the Furin/TGF-β1/Smad axis to promote epithelial-mesenchymal transition in pancreatic cancer cells.
    Oncogenesis (IF 6.119) Pub Date : 2020-08-26
    Huizhi Wang,Jie Li,Junbo He,Yawen Liu,Wen Feng,Hailang Zhou,Meng Zhou,Hong Wei,Ying Lu,Wanxin Peng,Fengyi Du,Aihua Gong,Min Xu

    Methyl-CpG-binding protein 2 (MeCP2) has been characterized as an oncogene in several types of cancer. However, its precise role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Hence, this study aimed to evaluate the potential role of MeCP2 in pancreatic cancer progression. We found that MeCP2 was upregulated in pancreatic cancer tissues, enhanced migration, invasion, and proliferation

  • NRIP3 upregulation confers resistance to chemoradiotherapy in ESCC via RTF2 removal by accelerating ubiquitination and degradation of RTF2.
    Oncogenesis (IF 6.119) Pub Date : 2020-08-24
    Daqin Suo,Ling Wang,Tingting Zeng,Hui Zhang,Lei Li,Jinyun Liu,Jingping Yun,Xin-Yuan Guan,Yan Li

    Esophageal squamous cell carcinoma (ESCC) is a common malignant cancer worldwide. Despite recent improvements in surgical techniques and adjuvant therapies, the prognosis of patients with advanced ESCC remains poor. Resistance to chemoradiotherapy (CRT) remains a major cause of treatment failure for advanced ESCC patients. Here, we report that NRIP3 (nuclear receptor interacting protein 3) promotes

  • Tumour suppressor 15-hydroxyprostaglandin dehydrogenase induces differentiation in colon cancer via GLI1 inhibition.
    Oncogenesis (IF 6.119) Pub Date : 2020-08-19
    Shakti Ranjan Satapathy,Geriolda Topi,Janina Osman,Karin Hellman,Fredrik Ek,Roger Olsson,Wondossen Sime,Lubna M Mehdawi,Anita Sjölander

    Inflammation is an established risk factor for colorectal cancer. We and others have shown that colorectal cancer patients with elevated cysteinyl leukotriene receptor 2 (CysLT2R) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) levels exhibit good prognoses. However, both CysLT2R and 15-PGDH, which act as tumour suppressors, are often suppressed in colorectal cancer. We previously reported that

  • New preclinical models for angioimmunoblastic T-cell lymphoma: filling the GAP.
    Oncogenesis (IF 6.119) Pub Date : 2020-08-14
    Rana Mhaidly,Adrien Krug,Philippe Gaulard,François Lemonnier,Jean-Ehrland Ricci,Els Verhoeyen

    Mouse models are essential to study and comprehend normal and malignant hematopoiesis. The ideal preclinical model should mimic closely the human malignancy. This means that these mice should recapitulate the clinical behavior of the human diseases such as cancer and therapeutic responses with high reproducibility. In addition, the genetic mutational status, the cell phenotype, the microenvironment

  • Targeting PD-L1 in non-small cell lung cancer using CAR T cells.
    Oncogenesis (IF 6.119) Pub Date : 2020-08-13
    Ming Liu,Xu Wang,Wei Li,Xinfang Yu,Pedro Flores-Villanueva,Zijun Y Xu-Monette,Ling Li,Mingzhi Zhang,Ken H Young,Xiaodong Ma,Yong Li

    Antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the landscape of therapies for non-small cell lung carcinoma (NSCLC); however, the majority of patients do not respond to these agents. In addition, hyperprogressive disease (HPD) develops in a larger portion of NSCLC patients treated with PD-1/PD-L1 inhibitors than in patients treated with standard

  • Reduction of SCUBE3 by a new marine-derived asterosaponin leads to arrest of glioma cells in G1/S.
    Oncogenesis (IF 6.119) Pub Date : 2020-08-06
    Peng-Cheng Qiu,Yun-Yang Lu,Shan Zhang,Hua Li,Han Bao,Yu-Qiang Ji,Fei Fang,Hai-Feng Tang,Guang Cheng

    Many saponins are characterized as exhibiting a wide spectrum of antitumor activities at low concentrations. Most of the previous studies that aimed to understand the mechanisms underlying anticancer saponins have focused on numerous classical signaling pathways. However, at the oncogene level, little is known about the action of saponins, especially asterosaponin. In this study, CN-3, a new asterosaponin

  • AUF1 promotes stemness in human mammary epithelial cells through stabilization of the EMT transcription factors TWIST1 and SNAIL1.
    Oncogenesis (IF 6.119) Pub Date : 2020-08-05
    Manar M AlAhmari,Huda H Al-Khalaf,Falah H Al-Mohanna,Hazem Ghebeh,Abdelilah Aboussekhra

    The AU-rich element RNA-binding protein 1 (AUF1) is an RNA-binding protein, which can both stabilize and destabilize the transcripts of several cancer-related genes. Since epithelial-to-mesenchymal transition (EMT) and the acquisition of cancer stem cell traits are important for cancer onset and progression, we sought to determine the role of AUF1 in these two important processes. We have shown that

  • The identification of nuclear αvβ3 integrin in ovarian cancer: non-paradigmal localization with cancer promoting actions.
    Oncogenesis (IF 6.119) Pub Date : 2020-07-29
    Chen Seraya-Bareket,Avivit Weisz,Elena Shinderman-Maman,Sharon Teper-Roth,Dina Stamler,Nissim Arbib,Yfat Kadan,Ami Fishman,Debora Kidron,Evgeny Edelstein,Martin Ellis,Osnat Ashur-Fabian

    Nuclear translocation of transmembrane proteins was reported in high-grade serous ovarian cancer (HGSOC), a highly aggressive gynecological malignancy. Although the membrane receptor αvβ3 integrin is amply expressed in HGSOC and involved in disease progression, its nuclear localization was never demonstrated. Nuclear αvβ3 was explored in HGSOC cells (OVCAR3, KURAMOCHI, and JHOS4), nuclear localization

  • Cyclin D1 targets hexokinase 2 to control aerobic glycolysis in myeloma cells.
    Oncogenesis (IF 6.119) Pub Date : 2020-07-24
    M Caillot,J Bourgeais,H Dakik,É Costé,N M Mazure,É Lelièvre,O Coqueret,O Hérault,F Mazurier,B Sola

    Cancer cells are characterized by the Warburg effect, a shift from mitochondrial respiration to oxidative glycolysis. We report here the crucial role of cyclin D1 in promoting this effect in a cyclin-dependent kinase (CDK)4/6-independent manner in multiple myeloma (MM) cells. We show that the cyclin D1 oncoprotein targets hexokinase 2 (HK2), a major glycolysis regulator, through two original molecular

  • Suppressing DRP1-mediated mitochondrial fission and mitophagy increases mitochondrial apoptosis of hepatocellular carcinoma cells in the setting of hypoxia.
    Oncogenesis (IF 6.119) Pub Date : 2020-07-13
    Xia-Hui Lin,Bai-Quan Qiu,Min Ma,Rui Zhang,Shu-Jung Hsu,Hua-Hua Liu,Jun Chen,Dong-Mei Gao,Jie-Feng Cui,Zheng-Gang Ren,Rong-Xin Chen

    Transarterial embolization/transarterial chemoembolization (TAE/TACE) is the acceptable palliative treatment for hepatocellular carcinoma (HCC), mainly through ischemic necrosis induced by arterial embolization. However, how HCC cells survive under such ischemic hypoxic condition remains unclear, which can be exploited to potentiate TAE/TACE treatment. We hypothesized that targeting mitophagy can increase

  • Exploring and modelling colon cancer inter-tumour heterogeneity: opportunities and challenges.
    Oncogenesis (IF 6.119) Pub Date : 2020-07-09
    Joyce Y Buikhuisen,Arezo Torang,Jan Paul Medema

    Colon cancer inter-tumour heterogeneity is installed on multiple levels, ranging from (epi)genetic driver events to signalling pathway rewiring reflected by differential gene expression patterns. Although the existence of heterogeneity in colon cancer has been recognised for a longer period of time, it is sparingly incorporated as a determining factor in current clinical practice. Here we describe

  • CXCL5 promotes gastric cancer metastasis by inducing epithelial-mesenchymal transition and activating neutrophils.
    Oncogenesis (IF 6.119) Pub Date : 2020-07-06
    Zheying Mao,Jiahui Zhang,Yinghong Shi,Wei Li,Hui Shi,Runbi Ji,Fei Mao,Hui Qian,Wenrong Xu,Xu Zhang

    Deregulated expression of chemokines in tumor microenvironment contributes to tumor metastasis by targeting distinct cells. Epithelial-derived neutrophil-activating peptide-78 (ENA78/CXCL5) is upregulated in many cancers and involved in tumor progression. The role and underlying mechanism of CXCL5 in gastric cancer (GC) metastasis remain unclear. In this study, we reported that the expression of CXCL5

  • BRN2 expression increases anoikis resistance in melanoma.
    Oncogenesis (IF 6.119) Pub Date : 2020-07-06
    Carly J Pierce,Jacinta L Simmons,Natasa Broit,Deshapriya Karunarathne,Mei Fong Ng,Glen M Boyle

    Melanoma tumors are highly heterogeneous, comprising of many cell populations that vary in their potential for growth and invasion. Differential transcription factor expression contributes to these phenotypic traits. BRN2, a member of the POU domain family of transcription factors is thought to play important roles in melanoma invasion and metastasis. However, the function of BRN2 during the metastatic

  • Galectin-9 promotes a suppressive microenvironment in human cancer by enhancing STING degradation.
    Oncogenesis (IF 6.119) Pub Date : 2020-07-06
    Chuan-Xia Zhang,Dai-Jia Huang,Valentin Baloche,Lin Zhang,Jing-Xiao Xu,Bo-Wen Li,Xin-Rui Zhao,Jia He,Hai-Qiang Mai,Qiu-Yan Chen,Xiao-Shi Zhang,Pierre Busson,Jun Cui,Jiang Li

    Galectin-9 (Gal-9) is known to enhance the expansion of myeloid-derived suppressor cells (MDSCs) in murine models. Its contribution to the expansion of MDSCs in human malignancies remain to be investigated. We here report that Gal-9 expression in nasopharyngeal carcinoma (NPC) cells enhances the generation of MDSCs (CD33+CD11b+HLA-DR−) from CD33+ bystander cells. The underlying mechanisms involve both

  • Histoepigenetic analysis of the mesothelin network within pancreatic ductal adenocarcinoma cells reveals regulation of retinoic acid receptor gamma and AKT by mesothelin.
    Oncogenesis (IF 6.119) Pub Date : 2020-07-02
    Eugene Lurie,Dongliang Liu,Emily L LaPlante,Lillian R Thistlethwaite,Qizhi Yao,Aleksandar Milosavljevic

    To enable computational analysis of regulatory networks within the cancer cell in its natural tumor microenvironment, we develop a two-stage histoepigenetic analysis method. The first stage involves iterative computational deconvolution to estimate sample-specific cancer-cell intrinsic expression of a gene of interest. The second stage places the gene within a network module. We validate the method

  • Regulation of invasion and peritoneal dissemination of ovarian cancer by mesothelin manipulation.
    Oncogenesis (IF 6.119) Pub Date : 2020-07-01
    Ricardo Coelho,Sara Ricardo,Ana Luísa Amaral,Yen-Lin Huang,Mariana Nunes,José Pedro Neves,Nuno Mendes,Mónica Nuñez López,Carla Bartosch,Verónica Ferreira,Raquel Portugal,José Manuel Lopes,Raquel Almeida,Viola Heinzelmann-Schwarz,Francis Jacob,Leonor David

    Peritoneal dissemination is a particular form of metastasis typically observed in ovarian cancer and the major cause for poor patient’s outcome. Identification of the molecular players involved in ovarian cancer dissemination can offer an approach to develop treatment strategies to improve clinical prognosis. Here, we identified mesothelin (MSLN) as a crucial protein in the multistep process of peritoneal

  • USP42 enhances homologous recombination repair by promoting R-loop resolution with a DNA-RNA helicase DHX9.
    Oncogenesis (IF 6.119) Pub Date : 2020-06-15
    Misaki Matsui,Ryo Sakasai,Masako Abe,Yusuke Kimura,Shoki Kajita,Wakana Torii,Yoko Katsuki,Masamichi Ishiai,Kuniyoshi Iwabuchi,Minoru Takata,Ryotaro Nishi

    The nucleus of mammalian cells is compartmentalized by nuclear bodies such as nuclear speckles, however, involvement of nuclear bodies, especially nuclear speckles, in DNA repair has not been actively investigated. Here, our focused screen for nuclear speckle factors involved in homologous recombination (HR), which is a faithful DNA double-strand break (DSB) repair mechanism, identified transcription-related

  • Myotubularin-related protein 7 activates peroxisome proliferator-activated receptor-gamma.
    Oncogenesis (IF 6.119) Pub Date : 2020-06-10
    Philip Weidner,Michaela Söhn,Torsten Schroeder,Laura Helm,Veronika Hauber,Tobias Gutting,Johannes Betge,Christoph Röcken,Florian N Rohrbacher,Vijaya R Pattabiraman,Jeffrey W Bode,Rony Seger,Daniel Saar,Ariane Nunes-Alves,Rebecca C Wade,Matthias P A Ebert,Elke Burgermeister

    Peroxisome proliferator-activated receptor-gamma (PPARγ) is a transcription factor drugable by agonists approved for treatment of type 2 diabetes, but also inhibits carcinogenesis and cell proliferation in vivo. Activating mutations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene mitigate these beneficial effects by promoting a negative feedback-loop comprising extracellular signal-regulated