Matrix Stiffness-Encoded Mechanical Memory Maintains Proliferative Dominance in Metastatic Tumors.

Matrix stiffness-encoded mechanical memory in metastatic tumor cells sustains malignant, proliferative traits by mitotically heritable epigenetic reprogramming, enabling continued advantage after detachment.

• Why it matters: Metastatic lesions face different microenvironments, yet retain similar phenotypes; clarifying how cells preserve this homogeneity could reveal ways to suppress metastasis.
• What they did: The study shows that matrix stiffness activates RhoA-ROCK1, remodeling actin and suppressing mitochondrial fission, which shifts mitochondrial dynamics toward fatty acid β-oxidation, acetyl-CoA buildup, and histone hyperacetylation.
• The result: Because the stiffness-driven epigenetic state is mitotically heritable, progeny retain proliferative advantage after leaving stiff matrices; blocking RhoA-ROCK1 disrupts mechanical memory and reduces metastasis.

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