PTPN9 induces cell apoptosis by mitigating the activation of Stat3 and acts as a tumor suppressor in colorectal cancer
Authors Wang D, Cheng Z, Zhao M, Jiao C, Meng Q, Pan H, Xie Y, Li L, Zhu Y, Wang W, Qu C, Liang D
Received 10 September 2018
Accepted for publication 8 January 2019
Published 8 February 2019 Volume 2019:11 Pages 1309—1319
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 4
Editor who approved publication: Professor Nakshatri
Dawei Wang,1,* Zhuoxin Cheng,2,3,* Ming Zhao,1,* Chengbin Jiao,2 Qinghui Meng,1 Huayang Pan,1 Yu Xie,1 Long Li,1 Yexing Zhu,1 Wei Wang,1 Chunlei Qu,1 Deshen Liang1
1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi 154002, People’s Republic of China; 3Heilongjiang Provincial Key Laboratory of Metabolic Disease, Jiamusi 154002, People’s Republic of China
*These authors contributed equally to this work
Background: Accumulating evidence has shown that protein tyrosine phosphatases (PTPs) are involved in regulating the transduction of many signaling pathways and play important roles in modulating the progression of some cancers, but the functions of PTPs in cancers have not been well elucidated until now. Here, we aimed to identify the roles of protein tyrosine phosphatase nonreceptor type 9 (PTPN9), a cytoplasmic PTP, in the development of colorectal cancer and elucidate the regulatory mechanism involved.
Materials and methods: Cell viability assessment, colony formation assay, caspase-3 and caspase-9 activity assay, real-time PCR, and Western blot analysis were applied.
Results: Our results showed that PTPN9 expression was frequently downregulated in colorectal cancer tissues compared with adjacent normal tissues. Overexpression of PTPN9 mitigated cell growth and colony formation and induced cell apoptosis in colorectal cancer. Conversely, PTPN9 knockdown promoted cell growth and survival. Moreover, PTPN9 negatively regulated the activation of Stat3 and depressed its nuclear translocation in colorectal cancer. The effects of PTPN9 knockdown on cell apoptosis were attenuated by inhibition of the Stat3 pathway.
Conclusion: These results indicate that PTPN9 inhibits cell growth and survival by repressing the activation of Stat3 in colorectal cancer, which suggests an important underlying mechanism of regulating cell growth and provides a novel candidate therapeutic target for colorectal cancer.
Keywords: PTPN9, apoptosis, colorectal cancer, Stat3, cell survival, PTPMeg2
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