2. Academic Validation
  3. SEC61G promotes colorectal cancer progression by regulating cytosolic Ca2+ concentration

SEC61G promotes colorectal cancer progression by regulating cytosolic Ca2+ concentration

  • J Gastroenterol. 2025 May 25. doi: 10.1007/s00535-025-02259-3.
Satoshi Higuchi 1 2,  Hajime Otsu 1,  Takaaki Masuda 3,  Masahiro Hashimoto 1 2,  Yusuke Nakano 1 2,  Kiyotaka Hosoda 1,  Kosuke Hirose 1,  Tomohiko Ikehara 1,  Takashi Ofuchi 1,  Yasuo Tsuda 1,  Yusuke Yonemura 1,  Mamoru Uemura 2,  Hidetoshi Eguchi 2,  Yuichiro Doki 2,  Koshi Mimori 4
Affiliations

Affiliations

  • 1 Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumibaru, Beppu, Oita, 874-0838, Japan.
  • 2 Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • 3 Department of Breast and Endocrine Surgery, Kochi University, Kochi, Japan.
  • 4 Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumibaru, Beppu, Oita, 874-0838, Japan. mimori.koshi.791@m.kyushu-u.ac.jp.
PMID: 40413702 DOI: 10.1007/s00535-025-02259-3
Abstract

Background: Intracellular calcium (CA2+) signaling regulates key Cancer processes. Research findings suggest that the Sec61 complex, involved in protein translocation, contributes to calcium leakage from the endoplasmic reticulum. However, the mechanism by which Sec61 Translocon Subunit Gamma (SEC61G), a component of this complex, influences colorectal Cancer (CRC) progression remains unclear.

Methods: Bioinformatics analysis was performed using The Cancer Genome Atlas data sets to identify candidate genes on chromosome 7p, examine their association with DNA copy number amplification. In addition, SEC61G expression in CRC cells and tissues was validated using reverse-transcription quantitative polymerase chain reaction and immunohistochemistry. Moreover, in vitro and in vivo experiments were performed to investigate the effects of SEC61G overexpression and knockdown on CRC cell proliferation. Furthermore, publicly available single-cell RNA Sequencing (scRNA-seq) and spatial transcriptome Sequencing (ST-seq) data were used to validate the role of SEC61G in CRC.

Results: SEC61G was significantly upregulated in CRC tissues and was correlated with poor prognosis in patients with CRC. SEC61G overexpression enhanced cell proliferation and activated the EGFR pathway, promoting cell cycle progression from the G1 to S phase. In addition, SEC61G overexpression increased cytosolic CA2+ levels, which activated EGFR signaling via Calmodulin. Moreover, analyses of scRNA-seq and ST-seq data confirmed that SEC61G expression was higher in tumor epithelial cells and that it was co-expressed with EGFR pathway-related genes.

Conclusions: SEC61G promotes CRC progression by regulating cytosolic CA2+ concentration, EGFR activation, and cell cycle progression, highlighting its potential as a prognostic biomarker and therapeutic target in CRC.

Keywords

Calcium; Colorectal cancer; Endoplasmic reticulum (ER); Epidermal growth factor receptor (EGFR); SEC61 Translocon subunit gamma (SEC61G).

Figures
Products