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Updated: Jun 22, 2025

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
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The adhesion-GPCR ADGRF5 fuels breast cancer progression by suppressing the MMP8-mediated antitumorigenic effects

Yalan Wu1, Huixia Liu2, Zhe Sun3

  • 1Department of Histology and Embryology, School of Basic Medical Sciences, Xiangya School of Medicine, Central South University, Changsha, 410013, China.

Cell Death & Disease
|June 27, 2024
PubMed

Insights

Loss of ADGRF5 in breast cancer hinders cell motility and growth by increasing antitumor MMP8. This promotes an anti-cancer immune response in the tumor microenvironment.

Area of Science:

  • Oncology
  • Cell Biology
  • Immunology

Background:

  • Adhesion G protein-coupled receptor F5 (ADGRF5), also known as GPR116, is implicated in breast cancer cell migration and metastasis.
  • The precise molecular mechanisms by which ADGRF5 influences breast cancer progression are not fully understood.

Purpose of the Study:

  • To elucidate the role of ADGRF5 in breast cancer cell motility, metastasis, and tumor growth.
  • To investigate the molecular pathways linking ADGRF5 to the tumor microenvironment (TME) and immune cell polarization.

Main Methods:

  • Investigated the impact of ADGRF5 absence on breast cancer cell migration and in vivo tumor growth.
  • Analyzed the expression of matrix metalloproteinase 8 (MMP8) and tumor-associated neutrophils (TANs) in the TME.
  • Utilized molecular assays to explore the ADGRF5-ERK1/2-RhoA-C/EBPβ signaling axis.
  • Identified C/EBPβ binding motifs in the MMP8 promoter region.

Main Results:

  • ADGRF5 absence impaired extracellular matrix (ECM)-associated cell motility and reduced in vivo tumor growth.
  • Heightened MMP8 expression and a shift towards antitumor N1 TAN polarization were observed in ADGRF5-deficient tumors.
  • ADGRF5 inhibited ERK1/2 activity via RhoA activation, suppressing C/EBPβ phosphorylation and nuclear translocation.
  • Silencing ADGRF5 increased MMP8 expression and CXCL8 secretion, enhancing TAN infiltration and promoting N1 polarization.

Conclusions:

  • ADGRF5 negatively regulates MMP8 expression and C/EBPβ activation, thereby controlling breast cancer cell motility and TME composition.
  • MMP8 contributes to TGF-β inactivation and N1 TAN polarization, opposing TGF-β-driven pro-metastatic effects.
  • ADGRF5 represents a novel therapeutic target for modulating the TME and inhibiting breast cancer progression.

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