YAP inhibits autophagy and promotes progression of colorectal cancer via upregulating Bcl-2 expression

Colorectal cancer (CRC) is one of the most aggressive and lethal cancers. The role of autophagy in the pathobiology of CRC is intricate, with opposing functions manifested in different cellular contexts. The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor-suppressor pathway, functions as an oncoprotein in a variety of cancers. In this study, we found that YAP could negatively regulate autophagy in CRC cells, and consequently, promote tumor progression of CRC in vitro and in vivo. Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.

Automated summary

Colorectal cancer is a highly aggressive and lethal cancer, with autophagy playing a complex role in its pathobiology. The transcriptional coactivator YAP has been found to negatively regulate autophagy in CRC cells, promoting tumor progression by upregulating the apoptosis-inhibitory protein Bcl-2 through TEAD interaction, thereby suppressing autophagy-related cell death. Targeting the YAP/Bcl-2 pathway may hold promise as a potential therapeutic strategy against CRC.