Functional analysis of mutant p53 on cancer invasion and metastasis using innovative in vivo imaging

众所周知，p53和TGF-β信号传导是调节细胞停滞和细胞凋亡的肿瘤抑制因子，而突变型p53和TGF-β信号传导在癌症转移中的关键作用现在已经出现。在本项目中，我们发现原癌蛋白Ski是TGF-β信号的重要负调控因子，它与p53相互作用，减弱p53的生物学功能，并可能成为一个特别有价值的治疗靶点。此外，我们发现组蛋白甲基转移酶SET 8抑制p53的生物学功能，也负调节TGF-β信号传导。

p53 and TGF-βsignaling are well known as tumor suppressors which regulate cytostasis and apoptosis, whereas critical roles of mutant p53 and TGF-βsignaling in cancer metastasis have now emerged. In this project, we have demonstrated that proto-oncoprotein Ski, which is an important negative regulator of TGF-βsignaling, interacts with p53 and attenuates the biological functions of p53.Moreover, we have shown that Ski may prove to be an especially valuable therapeutic target. Also, we identified that histone methyltransferase SET8, which represses the biological functions of p53, also negatively regulates TGF-βsignaling.