2. Academic Validation
  3. ESRP1-driven alternative splicing of CLSTN1 inhibits the metastasis of gastric cancer

ESRP1-driven alternative splicing of CLSTN1 inhibits the metastasis of gastric cancer

  • Cell Death Discov. 2023 Dec 19;9(1):464. doi: 10.1038/s41420-023-01757-8.
Chengguo Li # 1,  Yuping Yin # 1,  Ruikang Tao 2,  Yao Lin 1,  Tao Wang 1,  Qian Shen 1,  Runze Li 1,  Kaixiong Tao 3,  Weizhen Liu 4
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Center for Biomolecular Science and Engineering, University of California, Santa Cruz, CA, 95064, USA.
  • 3 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. [email protected].
  • 4 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. [email protected].
  • # Contributed equally.
PMID: 38114495 DOI: 10.1038/s41420-023-01757-8
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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