RING finger protein 38 induces gastric cancer cell growth by decreasing the stability of the protein tyrosine phosphatase SHP-1

Jigang Zhang; Hao Wu; Bin Yi; Jian Zhou; Luxin Wei; Yan Chen; Lifeng Zhang

doi:10.1002/1873-3468.13225

RING finger protein 38 induces gastric cancer cell growth by decreasing the stability of the protein tyrosine phosphatase SHP-1

FEBS Lett. 2018 Sep;592(18):3092-3100. doi: 10.1002/1873-3468.13225. Epub 2018 Aug 29.

Authors

Jigang Zhang¹, Hao Wu¹, Bin Yi², Jian Zhou², Luxin Wei², Yan Chen², Lifeng Zhang²

Affiliations

¹ Department of Emergency Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

PMID: 30112836
DOI: 10.1002/1873-3468.13225

Abstract

The function of the E3 ligase RNF38 is still unknown in gastric cancer. Here, we found that RNF38 is upregulated in gastric cancer, and it is associated with the overall survival of gastric cancer patients. Further studies showed that RNF38 interacts with the nonreceptor tyrosine phosphatase SH2-containing protein tyrosine phosphatase 1 (SHP-1) and induces the polyubiquitination of SHP-1, which leads to destabilization of SHP-1 and promotion of STAT3 signaling in gastric cancer cells. In addition, overexpression or knockdown of RNF38 induces or suppresses gastric cancer cell growth in vitro, respectively, and silencing RNF38 delays tumor growth in vivo. These findings demonstrate that RNF38 is functional in gastric cancer and promotes STAT3 signaling by destabilizing SHP-1; thus, RNF38 could be a novel target for gastric cancer therapy.

Keywords: RING finger protein 38; SHP-1; STAT3; cell growth; gastric cancer.

Publication types

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

MeSH terms

Animals
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Proliferation / genetics*
Cycloheximide / pharmacology
Gene Expression Regulation, Neoplastic / drug effects
Humans
Kaplan-Meier Estimate
Mice, Nude
Protein Stability / drug effects
Protein Synthesis Inhibitors / pharmacology
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics*
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
RNAi Therapeutics / methods
Stomach Neoplasms / genetics*
Stomach Neoplasms / metabolism
Stomach Neoplasms / therapy
Ubiquitination / drug effects
Xenograft Model Antitumor Assays / methods*

Substances

Carrier Proteins
Protein Synthesis Inhibitors
RNF38 protein, human
Cycloheximide
PTPN6 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 6