Related Experiment Video For Cutaneous squamous cell carcinoma
Updated: Mar 20, 2026

Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion
Published on: March 18, 2014
Extracellular matrix stiffness drives cutaneous squamous cell carcinoma malignant progression via YAP-dependent
Yuqing Feng1, Tong Zhou2, Cong Yan2
1Department of Dermatology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; The Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Abstract:
The extracellular matrix (ECM) stiffness is significantly elevated in cutaneous squamous cell carcinoma (cSCC) and positively correlates with Clark level, tumor thickness and poor disease-free survival, implicating ECM stiffness as a driver of cSCC malignant progression. Using clinical samples, hydrogels of different stiffness, and a mouse xenograft model, we demonstrated that ECM stiffening activates the integrin-FAK-YAP mechanotransduction pathway. This activation promotes YAP nuclear translocation and YAP-TEAD1 complex formation, which in turn enhances the transcription of the glycolytic enzyme PKM2. Consequently, PKM2 upregulation drives aerobic glycolysis in cSCC cells, leading to increased proliferation, migration, apoptosis resistance, and EMT progression. Therapeutic inhibition of ECM stiffness, YAP transcriptional activity or glycolysis markedly reduces tumor growth and malignant behaviors in vivo. These findings identify a critical mechano-metabolic signaling cascade driving cSCC malignant progression, providing novel targets for therapeutic intervention against cancers associated with fibrosis and mechanical stress.
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