Abstract
Metastasis is the main cause of cancer-related mortality. Although the actual process of metastasis remains largely elusive, epithelial-mesenchymal transition (EMT) has been considered as a major event in metastasis. Besides, hypoxia is common in solid cancers and has been considered as an important factor for adverse treatment outcomes including metastasis. Since EMT and hypoxia potentially share several signaling pathways, many recent studies focused on investigate the issue of hypoxia-induced EMT. Among all potential mediators of hypoxia-induced EMT, hypoxia-inducible factor-1α (HIF-1α) has been studied extensively. Moreover, there are other potential mediators that may also contribute to the process. This review aims to summarize the recent reports on hypoxia-induced EMT by HIF-1α or other potential mediators and provide insights for further investigations on this issue. Ultimately, better understanding of hypoxia-induced EMT may allow us to develop anti-metastatic strategies and improve treatment outcomes.
Highlights
Metastasis is the major cause of cancer-associated deaths [1]
Studies in the field of cancer biology have linked these two important tumorigenesis events together when unraveling the process of metastasis [8]
This study showed the elevation of Snail mRNA expression level after hypoxia-inducible factor-1α (HIF-1α) stabilization accompanied with E-cadherin repression plus vimentin and N-cadherin up-regulation
Summary
Metastasis is the major cause of cancer-associated deaths [1]. It is a sequential event of uncontrolled cell proliferation, angiogenesis, detachment, motility, invasion into bloodstream, settle in the microvasculature, and extravasation from the blood vessel and proliferation in secondary sites. It is a complicated process involving multiple genes and signaling pathways for each step [2,3,4]. Among different hypoxia-related pathways, hypoxia-inducible factor-1α (HIF-1α) has been studied extensively [9]. We summarize previous researches and recent findings of the effect of hypoxia on EMT induction with emphasis in various hypoxia-related mediators
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