Deficiency in SPOP-mediated ubiquitination and degradation of TIAM1 promotes gastric cancer progression

Fang Liu; Tong Zhang; Xiumei Sun; Zuolong Liu; Wei Xu; Xiangpeng Dai; Xiaoling Zhang

doi:10.1016/j.bbadis.2024.167032

Deficiency in SPOP-mediated ubiquitination and degradation of TIAM1 promotes gastric cancer progression

Biochim Biophys Acta Mol Basis Dis. 2024 Mar;1870(3):167032. doi: 10.1016/j.bbadis.2024.167032. Epub 2024 Jan 19.

Authors

Fang Liu¹, Tong Zhang², Xiumei Sun¹, Zuolong Liu¹, Wei Xu³, Xiangpeng Dai⁴, Xiaoling Zhang⁵

Affiliations

¹ Department of Emergency, First Hospital of Jilin University, Changchun, China.
² Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University, Changchun, China; National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital of Jilin University, Changchun, China.
³ Department of The Clinical Laboratory, First Hospital of Jilin University, Changchun, China. Electronic address: xu_w@jlu.edu.cn.
⁴ Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University, Changchun, China; National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital of Jilin University, Changchun, China. Electronic address: daixiangpeng@jlu.edu.cn.
⁵ Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University, Changchun, China; National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital of Jilin University, Changchun, China. Electronic address: xiaolingzhang@jlu.edu.cn.

PMID: 38246227
DOI: 10.1016/j.bbadis.2024.167032

Abstract

It was well known that SPOP is highly mutated in various cancers especially the prostate cancer and SPOP mutation dramatically impaired its tumor suppressive function. However, the detailed role and underlying mechanisms of SPOP in regulating the growth of gastric cancer is not fully studied. Here, we found that Cullin3^SPOP promoted the ubiquitination and degradation of TIAM1 protein in gastric cancer setting. Gastric cancer and prostate cancer derived SPOP mutation failed to suppress the proliferation, migration and invasion of gastric cancer cells partially due to the elevated level of TIAM1 protein. Notably, SPOP protein were negatively associated with TIAM1 protein in human gastric cancer tissue specimens. In conclusion, our results elucidate a molecular mechanism by which SPOP regulates the stability of TIAM1, and further demonstrate that SPOP inhibits the progression of gastric cancer by promoting the ubiquitination and degradation of TIAM1 protein.

Keywords: Degradation; Gastric cancer; SPOP; TIAM1; Ubiquitination.

Publication types

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

MeSH terms

Humans
Male
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Prostatic Neoplasms* / pathology
Repressor Proteins / genetics
Repressor Proteins / metabolism
Stomach Neoplasms* / genetics
T-Lymphoma Invasion and Metastasis-inducing Protein 1 / genetics
T-Lymphoma Invasion and Metastasis-inducing Protein 1 / metabolism
Ubiquitination

Substances

Repressor Proteins
T-Lymphoma Invasion and Metastasis-inducing Protein 1
Nuclear Proteins
SPOP protein, human
TIAM1 protein, human