Nanomechanical phenotyping uncovers a non-canonical smooth muscle-like hypercontractility program in lung squamous cell carcinoma myofibroblasts

LUSC myofibroblast-like cancer-associated fibroblasts show SMC-like hypercontractility with enhanced SM-MHC(MYH11) and ERK1/2-RLC hyperactivation despite reduced ROCK-MYPT1 signaling.

• Why it matters: myCAFs shape the stiff, tumor-promoting microenvironment, but their subtype-specific mechanical programs in NSCLC are not well defined, limiting mechanistic and therapeutic targeting.
• What they did: myCAFs from LUAD and LUSC were profiled using atomic force microscopy and traction force microscopy alongside molecular and signaling analyses, including SM-MHC(MYH11), ERK1/2-RLC, ROCK-MYPT1, and DNA methylation reprogramming.
• The result: LUSC-myCAFs amplified nanomechanical features and linked SMC-like markers to reduced proliferative capacity and smaller intratumoral vessel lumens, with SMC marker enrichment associated with adverse outcomes selectively in LUSC.

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