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Updated: Feb 15, 2026

Techniques to Induce and Quantify Cellular Senescence
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Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

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LRP6 targeting suppresses gastric tumorigenesis via P14ARF-Mdm2-P53-dependent cellular senescence

Haibin Wang1, Guoxing Xu2, Zhengjie Huang1,3

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

Oncotarget
|January 18, 2018
PubMed

Insights

NLRP6 (Nod-like receptor family, pyrin domain containing 6) acts as a tumor suppressor in gastric cancer. Its down-regulation correlates with poor survival, and restoring NLRP6 induces cancer cell cycle arrest and senescence.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • NLRP6 (Nod-like receptor family, pyrin domain containing 6) is known for its protective role in intestinal injury and colitis-associated colon cancer.
  • The precise cellular mechanisms underlying NLRP6-mediated protection, particularly in gastric cancer, are not fully understood.

Purpose of the Study:

  • To investigate the role of NLRP6 in gastric cancer development and progression.
  • To elucidate the cellular mechanisms by which NLRP6 influences gastric cancer cell behavior.

Main Methods:

  • Analysis of NLRP6 expression in primary gastric cancer tissues.
  • In vitro and in vivo functional studies involving ectopic NLRP6 overexpression or down-regulation.
  • Cell cycle analysis, western blotting, and assessment of senescence pathways (P14ARF-P53, NF-κB(p65), Mdm2).

Main Results:

  • NLRP6 was down-regulated in approximately 75% of gastric cancer cases, associated with lymph node metastasis and poor survival.
  • NLRP6 overexpression or down-regulation inhibited gastric cancer cell proliferation by inducing G1 phase cell cycle arrest via P21 and Cyclin D1.
  • Activation of the P14ARF-P53 pathway was crucial for NLRP6-induced cellular senescence, further enhanced by NF-κB(p65) and Mdm2 inactivation.

Conclusions:

  • NLRP6 functions as a negative regulator of gastric cancer.
  • Restoring NLRP6 expression can induce gastric cancer cell senescence, presenting a potential therapeutic strategy.
Keywords:
NLRP6P14ARFP53gastric cancersenescence

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