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

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

Cancer letters 2013 Feb 28

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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. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Citation

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. MAP3K10 promotes the proliferation and decreases the sensitivity of pancreatic cancer cells to gemcitabine by upregulating Gli-1 and Gli-2. Cancer letters. 2013 Feb 28;329(2):228-35