Mujcic H, Hill R P, Koritzinsky M, Wouters B G
Princess Margaret Cancer Centre and Campbell Family Institute for Cancer Research, University Health Network, 610 University Ave, Toronto, ON M5G 2M9, Canada.
Curr Mol Med. 2014;14(5):565-79. doi: 10.2174/1566524014666140603115831.
Conditions of poor oxygenation (hypoxia) are present in the majority of solid human tumors and are associated with poor patient prognosis due to both hypoxia-mediated resistance to treatment, and to hypoxia induced biological changes that promote increased malignancy, including metastasis. Tumor cells respond to hypoxia by activating several oxygen-sensitive signaling pathways that include the hypoxia inducible factor 1/2 (HIF1/2) signalling pathways and the unfolded protein response (UPR), which alter gene expression to promote adaptation and survival during hypoxic conditions. Furthermore, these hypoxia responsive pathways can lead to changes in gene expression and cellular phenotype that influence the potential of cancer cells to metastasize. However, the hypoxia-induced signaling events that promote tumor metastasis are still relatively poorly understood. Previous studies have largely focused on the contribution of the HIF signaling pathway to hypoxia-mediated metastasis. However, recent evidence demonstrates that hypoxic activation of the UPR is also an important mediator of metastasis.
大多数实体人类肿瘤中都存在氧合不足（缺氧）的情况，并且由于缺氧介导的治疗抗性以及缺氧诱导的促进恶性程度增加（包括转移）的生物学变化，导致患者预后不良。肿瘤细胞通过激活多种氧敏感信号通路来应对缺氧，这些信号通路包括缺氧诱导因子1/2（HIF1/2）信号通路和未折叠蛋白反应（UPR），它们会改变基因表达以促进在缺氧条件下的适应和存活。此外，这些缺氧反应通路可导致基因表达和细胞表型的变化，从而影响癌细胞转移的可能性。然而，促进肿瘤转移的缺氧诱导信号事件仍相对了解较少。先前的研究主要集中在HIF信号通路对缺氧介导转移的作用。然而，最近的证据表明，UPR的缺氧激活也是转移的重要介质。
