CTSG Suppresses Colorectal Cancer Progression through Negative Regulation of Akt/mTOR/Bcl2 Signaling Pathway

Int J Biol Sci. 2023 Apr 17;19(7):2220-2233. doi: 10.7150/ijbs.82000. eCollection 2023.


Colorectal cancer (CRC) is the most common gastrointestinal tumor worldwide, which is a severe malignant disease that threatens mankind. Cathepsin G (CTSG) has been reported to be associated with tumorigenesis, whereas its role in CRC is still unclear. This investigation aims to determine the function of CTSG in CRC. Our results indicated that CTSG was inhibited in CRC tissues, and patients with CTSG low expression have poor overall survival. Functional experiments revealed that CTSG overexpression suppressed CRC cell progression in vitro and in vivo, whereas CTSG suppression supports CRC development cells in vitro and in vivo. Mechanistically, CTSG overexpression suppressed Akt/mTOR signaling mechanism and elevated apoptotic-associated markers, and CTSG silencing activated Akt/mTOR signaling mechanisms and inhibited apoptotic-associated markers. Furthermore, the Akt suppression signaling pathway by MK2206 abolishes CTSG-silenced expression-induced cell viability and Bcl2 up-regulation in vitro and in vivo. Altogether, these outcomes demonstrate that CTSG may act as a tumor suppressor gene via Akt/mTOR/Bcl2-mediated anti-apoptotic signaling inactivation, and CTSG represents a potential therapeutic target in CRC.

Keywords: Akt; Bcl2; CTSG; colorectal cancer; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cathepsin G / genetics
  • Cathepsin G / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism


  • Proto-Oncogene Proteins c-akt
  • Cathepsin G
  • TOR Serine-Threonine Kinases
  • MTOR protein, human
  • CTSG protein, human
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2