GPR107: A key driver of breast cancer invasion and metastasis through collagen IV modulation

  • Cancer Gene Ther. 2025 Dec;32(12):1414-1427. doi: 10.1038/s41417-025-00977-7.
Ruyue Xu  1 ,  Jiahui Liang  2 ,  Shuyuan Zhang  3 ,  Puseletso Moru  1 ,  Kainan Liao  1 ,  Deping Xu  1 ,  Guodong Cao  4 ,  Chunlin Cai  5 ,  Dandan Zang  6 ,  Guoling Zhou  7 ,  Min Ren  8 ,  Haisheng Zhou  9  10
Affiliations
  • 1. Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, 230032, China.
  • 2. Department of Breast Surgery & Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, 230001, China.
  • 3. The First Clinical Medical College of Anhui Medical University, Hefei, 230001, China.
  • 4. Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, 230001, China.
  • 5. Department of Pathophysiology, Anhui Medical University, Hefei, 230032, China.
  • 6. Center for Scientific Research, Anhui Medical University, Hefei, 230032, China.
  • 7. Center for Computational Integrative Biology (CCIB), Massachusetts General Hospital (MGH), Harvard Medical Colleague, Boston, MA, USA.
  • 8. Department of Breast Surgery & Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, 230001, China. [email protected].
  • 9. Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, 230032, China. [email protected].
  • 10. Center for Scientific Research, Anhui Medical University, Hefei, 230032, China. [email protected].
PMID: 41073571 DOI: 10.1038/s41417-025-00977-7
Abstract

Breast Cancer is a leading cause of cancer-related death in women, and the development of effective treatments for advanced disease remains a critical challenge. Metastasis, the spread of Cancer cells to distant sites, is the major cause of mortality in breast Cancer. We identified a novel role for the G protein-coupled receptor 107 (GPR107) in promoting breast Cancer invasion and metastasis. Furthermore, we found that GPR107 mediates a reduction in Collagen Ⅳ (COL4), a key component of the extracellular matrix (ECM) that normally restricts tumor cell invasion. This reduction in COL4 levels was associated with GPR107 mediating the Clathrin-mediated endocytosis of COL4 from the ECM, an increase in matrix metalloproteinase 2 (MMP2) production to degrade COL4 in the ECM, and a decrease in COL4 production. Mechanistically, we identified GPR107 as a key mediator of the ERK/STAT3 pathway activation through β-arrestin, leading to increased expression of MMP2 and suppression of COL4 gene transcription, effectively promoting invasion and metastasis in breast Cancer cells. These findings suggest that GPR107 could serve as a promising biomarker for predicting breast Cancer malignancy and a potential therapeutic target for preventing and treating metastatic disease.

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