2. Academic Validation
  3. GSDMB interacts with IGF2BP1 to suppress colorectal cancer progression by modulating DUSP6-ERK pathway

GSDMB interacts with IGF2BP1 to suppress colorectal cancer progression by modulating DUSP6-ERK pathway

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113280. doi: 10.1016/j.intimp.2024.113280.
Haiyang Jiang 1,  Liting Deng 2,  Zexing Lin 3,  Kui Yang 4,  Jun Yang 4,  Wei Zhao 4,  Wenbin Gong 5
Affiliations

Affiliations

  • 1 Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; BenQ Medical Center, the Affiliated BenQ Hospital of Nanjing Medical University, Nanjing 210019, China.
  • 2 School of Medicine, Southeast University, Nanjing 210009, China.
  • 3 BenQ Medical Center, the Affiliated BenQ Hospital of Nanjing Medical University, Nanjing 210019, China.
  • 4 Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
  • 5 Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: gongwenbin177810@163.com.
PMID: 39353395 DOI: 10.1016/j.intimp.2024.113280
Abstract

There is growing evidence that the protein family of Gasdermins (GSDMs) play an essential role during the progression of colorectal Cancer (CRC). However, it is not completely clear that how GSDMB, abundantly expressed in epithelial cells of gastrointestinal tract, regulates the tumorigenesis of CRC. A wealth of evidence linking GSDMB to the pathogenesis of Cancer has come from genome-wide association studies. Here, we provide evidence that aberrantly upregulated GSDMB is responsible for suppressing the CRC progression by using in vitro cell and intestinal Organoid, as well as in vivo GSDMB transgenic mice models. Mechanistically, GSDMB interacts with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which directly binds to and recognizes the 3'-UTR of dual specificity Phosphatase 6 (DUSP6) mRNA, enhances the translation of DUSP6 protein and inhibits downstream ERK phosphorylation, thereby facilitating cell death and restraining cell proliferation. Our results suggest that GSDMB has potential as a novel therapeutic target for CRC treatment.

Keywords

Cell death; Cell proliferation; Colorectal cancer; GSDMB; IGF2BP1.

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