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Updated: Jun 16, 2026
06:35
A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
BRAF Inhibition-Associated Nuclear Remodeling is Linked to Cancer-Associated Fibroblast Activation
Jie Wang1, Bruna da Silva Soley1, Yao Xiao1
1Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio.
Cancer Research Communications
|June 15, 2026
Summary
Cancer-associated fibroblasts (CAFs) adapt to BRAF inhibition and matrix stiffness via a ROCK-dependent pathway. This mechanism involves cytoskeletal remodeling and nuclear changes, highlighting ROCK inhibition as a strategy against tumor-promoting CAF activation.
Area of Science:
- Oncology
- Cell Biology
- Biophysics
Background:
- Cancer-associated fibroblasts (CAFs) exhibit plasticity, adapting to the tumor microenvironment (TME) under stress.
- Understanding CAF adaptability is crucial for developing effective cancer therapies.
Purpose of the Study:
- To identify a shared pathway linking BRAF inhibition and matrix stiffness in CAFs.
- To elucidate the role of ROCK signaling in CAF mechanotransduction and activation.
Main Methods:
- Investigated BRAF inhibitor (BRAFi) effects on CAF signaling and cytoskeletal dynamics.
- Utilized varying substrate stiffness to mimic mechanical stress.
- Assessed nuclear deformation and β-catenin accumulation in CAFs.
- Employed pharmacological ROCK inhibition and constitutive β-catenin activation in mouse models.
Main Results:
- BRAFi and matrix stiffness converge on ROCK-dependent cytoskeletal remodeling and nuclear deformation in CAFs.
- This pathway leads to β-catenin nuclear accumulation and CAF activation.
- ROCK inhibition mitigates BRAFi- and stiffness-induced CAF responses.
- Constitutive β-catenin activation promotes CAF-like features and tumor growth in vivo.
Conclusions:
- A ROCK-cytoskeleton-nucleus axis mediates CAF responses to therapeutic and mechanical cues.
- Targeting this axis may limit tumor-promoting stromal adaptation during targeted therapy.
- ROCK inhibition presents a potential strategy to enhance cancer treatment efficacy.
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