Conclusions
SAV1 is a repressor during the development of human colorectal cancer by inhibiting the YAP-Akt-mTOR signalling pathway.
Methods
Human colorectal cancer samples were used to study the expression of SAV1 and YAP. Loss-of-function and gain-of-function strategies were used to study the effects of SAV1 on colorectal cancer cell growth. Rapamycin was used to treat cells and mice to investigate the effect of mTOR signalling.
Results
SAV1 represses the development of colorectal cancer by inhibiting the Akt-mTOR signalling in a YAP-dependent manner. The mRNA and protein levels of SAV1 are down-regulated in human colorectal cancer tissues compared with adjacent non-cancer tissues. SAV1 knockdown promotes the growth of colorectal cancer cells in vitro and in vivo, whereas SAV1 overexpression leads to opposing results. SAV1 represses the activation of the Akt-mTOR signalling, and rapamycin treatment blunts the effects of SAV1 on in vitro and in vivo growth of colorectal cancer cells. Finally, we show that SAV1 promotes the phosphorylation and inactivation of YAP, which contributes to the effect of SAV1 on Akt-mTOR signalling pathway. Conclusions: SAV1 is a repressor during the development of human colorectal cancer by inhibiting the YAP-Akt-mTOR signalling pathway.