Metformin attenuates PD-L1 expression through activating Hippo signaling pathway in colorectal cancer cells.

ABSTRACT: Programmed cell death ligand 1 (PD-L1) is a key suppressor of the cytotoxic immune response. In colorectal carcinoma (CRC), PD-L1 expression results in immune escape and poor prognosis. Extensive researches suggested that metformin had a potential efficacy of enhancing anti-tumor immune response in different types of cancer. However, the detail mechanisms underlying the efficacy in CRC are unclear. Here, we showed that metformin decreases PD-L1 and YAP1 expression in vitro and in vivo. After silencing or inhibiting YAP1 expression by Verteporfin (VP), the inhibitor of YAP1, the expression of PD-L1 were decreased in protein level in CRC cells. Furthermore, metformin directly phosphorylated YAP1 and restricted YAP1 to entry in the nucleus, so that PD-L1 was reduced via western blot and immun

SUBMITTER: Zhang JJ 

PROVIDER: S-EPMC6895520 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature