SIAH2 and neoplasm: It is possible that, the development of a hypoxic microenvironment during tumour growth leads to both of Siah2 and Zyxin activation through hypoxia and hypoxia-induced upregulation of TGF-β, respectively, which results in increased binding intensity of Lats2–Siah2 complex, thus allowing the efficient degradation of Lats2 and the activation of Yap (Fig. 8).