缺氧诱导的癌症上皮间质转化。
Hypoxia-induced epithelial to mesenchymal transition in cancer.
机构信息
Vanderbilt University, Nashville, TN, USA.
Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
出版信息
Cancer Lett. 2020 Sep 1;487:10-20. doi: 10.1016/j.canlet.2020.05.012. Epub 2020 May 26.
Abstract
A common feature of many solid tumors is low oxygen conditions due to inadequate blood supply. Hypoxia induces hypoxia inducible factor (HIF) stabilization and downstream signaling. This signaling has pleiotropic roles in cancers, including the promotion of cellular proliferation, changes in metabolism, and induction of angiogenesis. In addition, hypoxia is becoming recognized as an important driver of epithelial-to-mesenchymal (EMT) in cancer. During EMT, epithelial cells lose their typical polarized states and transition to a more mobile mesenchymal phenotype. Hypoxia induces this transition by modulating EMT signaling pathways, inducing EMT transcription factor activity, and regulating miRNA networks. As both hypoxia and EMT modulate the tumor microenvironment (TME) and are associated with immunosuppression, we also explore how these pathways may impact response to immuno-oncology therapeutics.
摘要
许多实体瘤的一个共同特征是由于血液供应不足导致的低氧条件。缺氧诱导缺氧诱导因子 (HIF) 稳定和下游信号转导。这种信号转导在癌症中具有多种作用，包括促进细胞增殖、代谢变化和诱导血管生成。此外，缺氧正被认为是癌症中上皮-间充质 (EMT) 的重要驱动因素。在 EMT 过程中，上皮细胞失去其典型的极化状态，并向更具迁移能力的间充质表型转化。缺氧通过调节 EMT 信号通路、诱导 EMT 转录因子活性和调节 miRNA 网络来诱导这种转化。由于缺氧和 EMT 都调节肿瘤微环境 (TME) 并与免疫抑制有关，我们还探讨了这些途径如何影响对免疫肿瘤治疗的反应。
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J Clin Oncol. 2020 Apr 10;38(11):1154-1163. doi: 10.1200/JCO.19.01598. Epub 2020 Jan 21.
2
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3
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7
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