Cancer-Associated Fibroblast-Derived FGF7 Promotes Clear Cell Renal Cell Carcinoma Progression and Macrophage...

Area of Science:

• Oncology
• Cancer Biology
• Molecular Mechanisms

Background:

• Cancer-associated fibroblasts (CAFs) are key stromal cells in clear cell renal cell carcinoma (ccRCC) microenvironments, known to support tumor growth.
• The precise molecular mechanisms by which CAFs promote ccRCC progression remain incompletely understood.

Purpose of the Study:

• To elucidate the molecular signaling pathways mediating the supportive role of CAFs in ccRCC.
• To identify potential therapeutic targets within the CAF-ccRCC tumor cell crosstalk.

Main Methods:

• Clustering consensus analysis and single-cell analysis were employed.
• Experimental validation was conducted, including in vivo studies using the RENCA mouse model.
• Mechanistic studies investigated signaling pathways like AKT and STAT3.

Main Results:

• CAF-derived FGF7 acts as a crucial signaling mediator between CAFs and ccRCC cells.
• FGF7 activates AKT signaling, promoting ccRCC cell growth and invasion.
• ccRCC cells induce STAT3-mediated FGF7 expression in CAFs, creating a feedback loop.
• FGF7 depletion in vivo reduced M2 macrophage infiltration and impeded tumor development.

Conclusions:

• A critical signaling axis involving CAF-derived FGF7 in ccRCC progression has been delineated.
• FGF7 promotes ccRCC growth and invasion through AKT activation and influences the tumor microenvironment by affecting M2 macrophage recruitment.
• FGF7 represents a promising therapeutic target for ccRCC treatment.