Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2018; 9:35512.

NLRP6 targeting suppresses gastric tumorigenesis via P14ARF–Mdm2–P53-dependent cellular senescence

Haibin Wang, Guoxing Xu, Zhengjie Huang, Weizheng Li, Huali Cai, Yunda Zhang, Disheng Xiong, Gang Liu, Shengjie Wang, Zengfu Xue _ and Qi Luo

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Oncotarget. 2017; 8:111597-111607. https://doi.org/10.18632/oncotarget.22876

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Abstract

Haibin Wang1,*, Guoxing Xu2,*, Zhengjie Huang1,3,*, Weizheng Li4, Huali Cai1, Yunda Zhang1, Disheng Xiong1, Gang Liu1, Shengjie Wang1, Zengfu Xue4 and Qi Luo1

1Department of Gastrointestinal Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian, China

2Department of Endoscopy Center, The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian, China

3Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350004, China

4Department of Cancer Prevention, Diagnosis and Treatment, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian, China

*These authors have contributed equally to this work

Correspondence to:

Zengfu Xue, email: zfxue@xmu.edu.cn

Qi Luo, email: luoqixmfh@126.com

Keywords: NLRP6; gastric cancer; senescence; P14ARF; P53

Received: July 17, 2017     Accepted: November 15, 2017     Published: December 04, 2017

ABSTRACT

NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo. Activation of the P14ARF-P53 pathway played a crucial role in the observed cellular senescence. We further demonstrated that ectopic overexpression of NLRP6 combined with inactivation of NF-κB(p65) and Mdm2 activates P14ARF-P53 to promote the senescence of gastric cancer cells. These findings indicate that NLRP6 functions as a negative regulator of gastric cancer and offer a potential new option for preventing gastric cancer.


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