MAP3K10 promotes the proliferation and decreases the sensitivity of pancreatic cancer cells to gemcitabine by upregulating Gli-1 and Gli-2

Yong An; Baobao Cai; Jianmin Chen; Nan Lv; Jie Yao; Xiaofeng Xue; Min Tu; Dong Tang; Jishu Wei; Kuirong Jiang; Junli Wu; Qiang Li; Wentao Gao; Yi Miao

doi:10.1016/j.canlet.2012.11.005

MAP3K10 promotes the proliferation and decreases the sensitivity of pancreatic cancer cells to gemcitabine by upregulating Gli-1 and Gli-2

Cancer Lett. 2013 Feb 28;329(2):228-35. doi: 10.1016/j.canlet.2012.11.005. Epub 2012 Nov 23.

Authors

Yong An¹, Baobao Cai, Jianmin Chen, Nan Lv, Jie Yao, Xiaofeng Xue, Min Tu, Dong Tang, Jishu Wei, Kuirong Jiang, Junli Wu, Qiang Li, Wentao Gao, Yi Miao

Affiliation

¹ Laboratory of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

PMID: 23178452
DOI: 10.1016/j.canlet.2012.11.005

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among 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 the expression status of MAP3K10 in PDAC tissues and cell lines, and analyzed the viability and cell proliferation of PDAC cells with an overexpression or knockdown of MAP3K10 in vitro. MAP3K10 was upregulated in PDAC tissues and cell lines. Overexpression of MAP3K10 promoted the proliferation and decreased the gemcitabine sensitivity of pancreatic cancer cells. In contrast, knockdown of MAP3K10 significantly decreased cell proliferation and sensitized cells to gemcitabine. However, neither overexpression nor knockdown of MAP3K10 affected cell migration. Moreover, overexpression of MAP3K10 resulted in upregulation of Gli-1 and Gli-2 in PDAC cells. Our results indicate a novel and important role for MAP3K10 in the proliferation and chemoresistance of PDAC. Our study suggests that targeting MAP3K10 is a potential strategy for the development of alternative therapies for pancreatic cancers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antimetabolites, Antineoplastic / pharmacology*
Apoptosis / drug effects
Carcinoma, Pancreatic Ductal / drug therapy
Carcinoma, Pancreatic Ductal / enzymology*
Carcinoma, Pancreatic Ductal / pathology
Cell Line, Tumor / drug effects
Cell Movement
Cell Proliferation
Cell Survival / drug effects
Deoxycytidine / analogs & derivatives*
Deoxycytidine / pharmacology
Drug Resistance, Neoplasm
Gemcitabine
Gene Expression / drug effects
Humans
Kruppel-Like Transcription Factors / genetics*
Kruppel-Like Transcription Factors / metabolism
MAP Kinase Kinase Kinases / genetics
MAP Kinase Kinase Kinases / metabolism*
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Pancreatic Neoplasms / drug therapy
Pancreatic Neoplasms / enzymology*
Pancreatic Neoplasms / pathology
Transcription Factors / genetics*
Transcription Factors / metabolism
Up-Regulation / drug effects
Zinc Finger Protein GLI1
Zinc Finger Protein Gli2

Substances

Antimetabolites, Antineoplastic
GLI1 protein, human
GLI2 protein, human
Kruppel-Like Transcription Factors
Nuclear Proteins
Transcription Factors
Zinc Finger Protein GLI1
Zinc Finger Protein Gli2
Deoxycytidine
MAP Kinase Kinase Kinases
MAP3K10 protein, human
Gemcitabine