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

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

  • Cancer Biother Radiopharm. 2021 Dec 31. doi: 10.1089/cbr.2021.0317.
Weijiang Wu 1 2 Hanqing Yang 3 4 Zhutao Wang 1 Zhijian Zhang 2 Xiaodong Lu 2 Wenjing Yang 2 Xiayue Xu 3 Yinuo Jiang 2 Yan Li 2 Xin Fan 3 Qixiang Shao 1 5
Affiliations

Affiliations

  • 1 Department of Immunology, Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, People's Republic of China.
  • 2 Department of Histology and Embryology, School of Medicine, Jiangsu University, Zhenjiang, People's Republic of China.
  • 3 Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, People's Republic of China.
  • 4 Department of Burns and Plastic Surgery, Wujin Hospital Affiliated to Jiangsu University, Changzhou, People's Republic of China.
  • 5 Jiangsu College of Nursing, School of Medical Science and Laboratory Medicine, Huai'an, People's Republic of China.
Abstract

Objective: Sonic Hedgehog (Shh)-Gli1 signaling and osteopontin (OPN) 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 OPN on human PDAC and assess whether Hh signaling affects pancreatic Cancer cells through upregulation of OPN. Materials and Methods: OPN expression in human PDAC tissues and cell lines was investigated. Proliferation, Apoptosis, migration, and invasion of OPN-knockdown BxPC-3 cells were observed. We analyzed the correlation between Shh or Gli1 and OPN expression in human PDAC. Hh signaling inhibitors and shRNA against Gli1 were used to confirm if OPN expression in BxPC-3 cells was regulated by Hh canonical or noncanonical pathway. We also evaluated the proliferation, Apoptosis, migration, and invasion of Gli1-knockdown BxPC-3 cells. Results: OPN 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 OPN was knocked down. Correlation analysis showed that Gli1, but not Shh, was associated with OPN expression in human PDAC, and Gli1 regulated OPN production in BxPC-3 cells through a noncanonical pathway because Gli but not Smo Inhibitor reduced OPN expression. Similar to above, the proliferation, migration, and invasion of BxPC-3 cells were decreased, whereas the Apoptosis was increased when Gli1 was knocked down. Supplement of exogenous OPN protein could partially reverse the effect of both OPN knockdown and Gli1 knockdown on the bio-behavior of BxPC-3 cells. Conclusion: Hh signaling promotes proliferation, migration, and invasion but inhibits Apoptosis of pancreatic Cancer cells through upregulation of OPN in a noncanonical pathway.

Keywords

Hedgehog; OPN; glioma-associated oncogene 1; pancreatic cancer.

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