Solid tumours invariably exhibit regions of hypoxia and up-regulation of receptor tyrosine kinases (RTKs) that trigger multiple signal pathways, including those that govern cell proliferation, survival and motility, ultimately contributing to oncogenesis. Although past studies have shown hypoxia-dependent transcriptional and translational induction of several RTK expression and their respective ligands, recent evidence suggests that hypoxia regulates RTK signalling through endocytosis, a major deactivation pathway of RTKs. Hypoxia-mediated endocytosis is also thought to modulate the activity of a growing list of other membrane-associated proteins such as integrins and Na,K-ATPase. These recent discoveries underscore the emergence of endocytosis as an important hypoxia-mediated regulatory process in cancer.
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