A Noncanonical Hedgehog Signaling Exerts a Tumor-Promoting Effect on Pancreatic Cancer Cells Via Induction of Osteopontin Expression.

Sonic Hedgehog (Shh)-Gli1 signaling and osteopontin () play vital roles in pancreatic cancer. However, the precise mechanisms of both signals have not been fully clarified, and whether there is a correlation between them in pancreatic ductal adenocarcinoma (PDAC) is unknown. This study aims to confirm the effect of on human PDAC and assess whether Hh signaling affects pancreatic cancer cells through upregulation of . expression in human PDAC tissues and cell lines was investigated. Proliferation, apoptosis, migration, and invasion of -knockdown BxPC-3 cells were observed. We analyzed the correlation between or and expression in human PDAC. Hh signaling inhibitors and shRNA against were used to confirm if expression in BxPC-3 cells was regulated by Hh canonical or noncanonical pathway. We also evaluated the proliferation, apoptosis, migration, and invasion of -knockdown BxPC-3 cells. is highly expressed in human PDAC tissues and cell lines. The proliferation, migration, and invasion of BxPC-3 cell lines were decreased, whereas apoptosis was increased when was knocked down. Correlation analysis showed that , but not , was associated with expression in human PDAC, and regulated production in BxPC-3 cells through a noncanonical pathway because but not Smo inhibitor reduced expression. Similar to above, the proliferation, migration, and invasion of BxPC-3 cells were decreased, whereas the apoptosis was increased when was knocked down. Supplement of exogenous OPN protein could partially reverse the effect of both knockdown and knockdown on the bio-behavior of BxPC-3 cells. Hh signaling promotes proliferation, migration, and invasion but inhibits apoptosis of pancreatic cancer cells through upregulation of in a noncanonical pathway.