2. Academic Validation
  3. GPR107: A key driver of breast cancer invasion and metastasis through collagen IV modulation

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

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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