CRISPR/Cas9-mediated knockout of SGLT1 inhibits proliferation and alters metabolism of gastric cancer cells

Min Shi; Chao Wang; Jun Ji; Qu Cai; Qianfu Zhao; Wenqi Xi; Jun Zhang

doi:10.1016/j.cellsig.2021.110192

CRISPR/Cas9-mediated knockout of SGLT1 inhibits proliferation and alters metabolism of gastric cancer cells

Cell Signal. 2022 Feb:90:110192. doi: 10.1016/j.cellsig.2021.110192. Epub 2021 Nov 12.

Authors

Min Shi¹, Chao Wang¹, Jun Ji², Qu Cai¹, Qianfu Zhao¹, Wenqi Xi³, Jun Zhang⁴

Affiliations

¹ Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, China.
² Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, China.
³ Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, China. Electronic address: xwq11061@rjh.com.cn.
⁴ Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai 200025, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: junzhang10977@sjtu.edu.cn.

PMID: 34774990
DOI: 10.1016/j.cellsig.2021.110192

Abstract

Background: The roles played by sodium/glucose cotransporters 1 (SGLT1) that transport glucose in cells independent of extracellular glucose concentration in gastric cancer are unknown.

Methods: The expression of SGLT1 in 75 primary gastric cancer and paired adjacent normal tissue specimens was determined. Also, the underlying mechanism of the altered SGLT1 expression and its impact on the proliferation of the gastric cancer cells and their metabolism were investigated.

Results: SGLT1 expression was found to be positively associated with pT, pN, TNM staging, histological differentiation, and a worse overall survival. CRISPR/Cas9 mediated knockout of SGLT1 could inhibit proliferation of gastric cancer cells, promote their apoptosis, and could also alter the metabolism of gastric cancer cells. Mechanistically, the transcription activity of SGLT1 could be negatively regulated by p53.

Conclusions: Besides identifying the important role of SGLT1 in gastric cancer, the underlying regulation mechanism in play was also elucidated. These make SGLT1 a promising new molecular target for the design of novel therapeutic modalities to control gastric cancer.

Keywords: Gastric cancer; Metabolism; Proliferation; SGLT1; Transcription regulation.

Publication types

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

MeSH terms

CRISPR-Cas Systems / genetics
Cell Proliferation / genetics
Glucose / metabolism
Humans
Stomach Neoplasms* / genetics

Substances

Glucose