TGF-β信号缺陷是否是人类癌症中的致命弱点?

Can Defective TGF-β Signaling Be an Achilles Heel in Human Cancer

癌细胞中的存活信号可激活mTOR-哺乳动物雷帕霉素靶蛋白。mTOR可抑制TGF-β信号,后者可使细胞周期停滞于G1后期,因此,活化后的mTOR可防止细胞周期停滞于TGF-β介导的检验点。雷帕霉素可重新激活TGF-β信号,从而导致G1期细胞停滞。在人类癌症中,TGF-β信号通常发生缺陷,相反,在雷帕霉素作用下,TGF-β信号缺陷的癌细胞不发生G1期停滞,而发生凋亡。因此,在基于雷帕霉素的抗癌治疗策略中,TGF-β信号缺陷可能是癌细胞的致命弱点。

Survival signals in cancer cells activate mTOR-the mammalian target of rapamycin, mTOR suppresses TGF-β signals that arrest cell cycle progression in late G1-thus activated mTOR prevents cell cycle arrest at a checkpoint mediated by TGF-β. Rapamycin treatment resurrects TGF-β signals causing G1 arrest. Defects in TGF-β signaling are common in human cancer, and ironically, cancer cells with defective TGF-β signaling that do not arrest in G1, instead undergo apoptosis when treated with rapamycin. Thus, defective TGF-β signaling may represent an Achilles heel for rational therapeutic targeting of cancer cells using rapamycin-based strategies.