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CAF-Driven EMT and ECM Remodeling Programs Promote Mesothelioma Progression
Licun Wu1,2, Hana Yun1,2, Hamed Yasavoli Sharahi1,2
1Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada.
Cancers
|August 13, 2026
Summary
Stromal cells drive mesothelioma progression and therapy resistance by regulating epithelial-mesenchymal transition (EMT). Targeting tumor-stroma signaling networks offers potential therapeutic strategies for mesothelioma.
Area of Science:
- Oncology
- Cancer Biology
- Tumor Microenvironment
Background:
- Mesothelioma progression involves tumor cell plasticity and complex interactions with the stromal microenvironment.
- Mechanisms of stromal regulation of epithelial-mesenchymal transition (EMT), tumor evolution, and therapeutic resistance in mesothelioma are not well understood.
Purpose of the Study:
- To identify stromal-EMT programs driving mesothelioma progression using integrated transcriptomic profiling and single-cell RNA sequencing.
- To investigate how fibroblast-to-tumor cell ratios influence transcriptional reprogramming and mesenchymal transition in vitro.
Main Methods:
- Longitudinal transcriptomic profiling and single-cell RNA sequencing in a murine intraperitoneal mesothelioma model (0-8 weeks).
- In vitro co-culture systems of fibroblasts and mesothelioma cells to study ratio-dependent effects.
Main Results:
- Identified eight distinct cancer-associated fibroblast (CAF) subtypes with specialized transcriptional programs.
- Revealed coordinated intercellular communication networks involving mesenchymal transition, fibrotic remodeling, and inflammatory crosstalk.
- Demonstrated that fibroblast signaling induces ratio-dependent EMT, promoting a shift towards mesenchymal phenotypes.
Conclusions:
- Stromal regulation of EMT is a key driver of mesothelioma progression, sarcomatoid transition, and therapy resistance.
- Tumor-stroma signaling networks represent potential therapeutic targets for mesothelioma treatment.
