Abstract

Pancreatic ductal adenocarcinoma (PDAC) isamong the most lethal human malignancies and is regulated by Sonic Hedgehog(Shh) signaling. Recently, MAP3K10 has been shown to regulate Shh signaling,suggesting a role for MAP3K10 in the tumorigenesis of PDAC. We determined theexpression status of MAP3K10 in PDAC tissues and cell lines, and analyzed theviability and cell proliferation of PDAC cells with an overexpression orknockdown of MAP3K10 in vitro. MAP3K10 was upregulated in PDAC tissues and celllines. Overexpression of MAP3K10 promoted the proliferation and decreased thegemcitabine sensitivity of pancreatic cancer cells. In contrast, knockdown ofMAP3K10 significantly decreased cell proliferation and sensitized cells togemcitabine. However, neither overexpression nor knockdown of MAP3K10 affectedcell migration. Moreover, overexpression of MAP3K10 resulted in upregulation ofGli-1 and Gli-2 in PDAC cells. Our results indicate a novel and important rolefor MAP3K10 in the proliferation and chemoresistance of PDAC. Our studysuggests that targeting MAP3K10 is a potential strategy for the development ofalternative therapies for pancreatic cancers.