2. Academic Validation
  3. SLC11A1 can activate TGF-β1 signaling pathway to resist ferroptosis in colorectal cancer

SLC11A1 can activate TGF-β1 signaling pathway to resist ferroptosis in colorectal cancer

  • Sci Rep. 2025 Dec 23. doi: 10.1038/s41598-025-32979-8.
DongQiang Yang 1,  LianMei Zhao 2,  Ping Shi 3,  Jianfeng Zhang 4,  Guang Yang 1,  Bo Shi 1,  Hongqing Ma 4,  Baokun Li 4,  Feifei Wang 4,  Guiying Wang 5 6 7
Affiliations

Affiliations

  • 1 Department of Radiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
  • 2 Scientific Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
  • 3 Otorhinolaryngology Head and Neck Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
  • 4 The Second Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
  • 5 The Second Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. [email protected].
  • 6 Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. [email protected].
  • 7 Hebei Key Laboratory of Etiology Tracing and Individualized Diagnosis and Treatment for Digestive System Carcinoma, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. [email protected].
PMID: 41436829 DOI: 10.1038/s41598-025-32979-8
Abstract

High expression of Solute Carrier Family 11 Member 1(SLC11A1) leads to a poor prognosis in patients with CRC, while the specific role of SLC11A1 in CRC remains unreported. Therefore, this study mainly addressed the preliminary mechanism and specific role of SLC11A1 in CRC. The results showed that six subsequent genes were successfully screened by the line database, and the abnormal expression of SLC11A1 was the most obvious in colorectal Cancer patients. Following phenotypic experiments demonstrated that SLC11A1 promoted proliferation, invasion and migration of colorectal Cancer cells. SLC11A1 Is also able to downregulate Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL 4), Cyclooxygenase-2 (COX2), NADPH Oxidase 1 (NOX1) and upregulate the expression levels of Hypoxia-Inducible Factor 1 (FIH1), Glutathione Peroxidase 1 (GPX1) protein, inhibit the expression levels of MDA and Fe2+ in colorectal Cancer cells, and resist Ferroptosis in colorectal Cancer cells. SLC11A1 Overexpression can up-regulate the protein expression level of TGFβ1 (Transforming Growth Factor Beta 1), p-Smad 2 / 3, activate TGFβ1 signaling pathway activity, and promote colorectal Cancer cell progression. In conclusion, we successfully demonstrated that SLC11A1 confers resistance to Ferroptosis in colorectal Cancer cells, providing a potential target for the clinical treatment of colorectal Cancer.

Keywords

Colorectal cancer; Ferroptosis; Invasion and metastasis; Solute carrier family 11 member 1; Transforming growth factor beta 1 signaling pathway.

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