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Epithelial-mesenchymal transition induction is associated with augmented glucose uptake and lactate production in pancreatic ductal adenocarcinoma
Cancer & Metabolism ( IF 5.9 ) Pub Date : 2016-10-17 , DOI: 10.1186/s40170-016-0160-x
Menghan Liu 1 , Lake-Ee Quek 2 , Ghazal Sultani 1 , Nigel Turner 1
Affiliation  

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a common malignancy with dismal prognosis. Metastatic spread and therapeutic resistance, the main causes of PDAC-related mortalities, are both partially underlined by the epithelial-mesenchymal transition (EMT) of PDAC cells. While the role of Warburg metabolism has been recognized in supporting rapid cellular growth and proliferation in many cancer types, less is known about the metabolic changes occurring during EMT, particularly in the context of PDAC.ResultsIn the current study, experimental models of EMT were established in the Panc-1 cell line of human PDAC via exposure to two physiologically relevant EMT inducers (tumor necrosis factor-α and transforming growth factor-β) and the metabolic consequences examined. The two EMT models displayed similar alterations in the general metabolic profile including augmented glucose uptake and lactate secretion as well as the lack of change in oxidative metabolism. Examination of molecular markers revealed differences in the pathways underlying the metabolic rewiring. 13C-Glucose tracer data confirmed that a major portion of accumulated lactate was derived from glucose, but subsequent flux analysis suggested involvement of non-canonical pathways towards lactate production.ConclusionsOur results characterize the metabolic reprogramming occurring during PDAC cell EMT and highlight the common changes of increased glucose uptake and lactate secretion under different EMT conditions. Such insight is urgently required for designing metabolic strategies to selectively target cells undergoing EMT in PDAC.

中文翻译:

上皮-间质转化诱导与胰腺导管腺癌中葡萄糖摄取和乳酸产生增加有关

背景胰腺导管腺癌(PDAC)是一种常见的恶性肿瘤,预后不佳。PDAC 细胞的上皮间质转化 (EMT) 部分强调了转移性扩散和治疗抵抗是 PDAC 相关死亡的主要原因。虽然 Warburg 代谢在支持多种癌症类型的细胞快速生长和增殖方面的作用已得到认可,但对 EMT 期间发生的代谢变化知之甚少,尤其是在 PDAC 的背景下。 结果在目前的研究中,建立了 EMT 的实验模型在人类 PDAC 的 Panc-1 细胞系中,通过暴露于两种生理相关的 EMT 诱导剂(肿瘤坏死因子-α 和转化生长因子-β)并检查代谢结果。两个 EMT 模型在一般代谢特征中显示出类似的变化,包括增加的葡萄糖摄取和乳酸分泌以及氧化代谢没有变化。分子标记的检查揭示了代谢重新布线的潜在途径的差异。13C-葡萄糖示踪剂数据证实,大部分积累的乳酸来自葡萄糖,但随后的通量分析表明参与乳酸产生的非经典途径。结论我们的结果表征了 PDAC 细胞 EMT 期间发生的代谢重编程,并突出了在不同 EMT 条件下增加葡萄糖摄取和乳酸分泌。迫切需要这种洞察力来设计代谢策略以选择性地靶向 PDAC 中经历 EMT 的细胞。
更新日期:2016-10-17
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