ESRP1-driven Alternative Splicing of CLSTN1 Inhibits the Metastasis of Gastric Cancer

Overview

Journal Cell Death Discov

Date 2023 Dec 19

PMID 38114495

Authors

Chengguo Li

Yuping Yin

Ruikang Tao

Yao Lin

Tao Wang

Qian Shen

Runze Li

Kaixiong Tao

Weizhen Liu

Affiliations

Soon will be listed here.

Abstract

Tumor metastasis severely limits the prognosis of gastric cancer patients. RNA-binding proteins (RBPs) are crucial in tumor metastasis, yet there is limited research into their involvement in gastric cancer. Here, we found that ESRP1, a RBP specific in epithelial cells, is important in regulating the metastasis of gastric cancer cells. ESRP1 is negatively correlated with distant metastasis and lymph node metastasis in gastric cancer patients. And we demonstrated that ESRP1 inhibit migration and invasion of gastric cancer in vitro and in vivo. Mechanistically, ESRP1 promotes exon 11 alternative splicing of CLSTN1 pre-mRNA. The post-splicing short CLSTN1 stabilizes the Ecadherin/β-catenin binding structure, and promotes β-catenin protein ubiquitination and degradation, thereby inhibiting the migration and invasion of gastric cancer cells. Our study highlights the role of ESRP1 in regulating metastasis of gastric cancer and extends its mechanism. These results provide a possibility for ESRP1 and CLSTN1 to become therapeutic targets for metastasis of gastric cancer.

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