975-Durotaxis as a Driver of Fibrosis and Cancer Metastasis

This research identifies durotaxis, the directional migration of cells toward stiffer tissues, as a critical driver of organ fibrosis and cancer metastasis. By using advanced mapping techniques, the authors demonstrate that diseased tissues create steep stiffness gradients that guide fibroblasts to injury sites and promote their transformation into scar-forming cells. In pancreatic cancer, these same mechanical cues encourage aggressive tumor cells to disseminate and spread to distant organs. The study pinpoints the FAK–paxillin molecular interaction as the essential "sensor" cells use to navigate these gradients. Both genetic modifications and a novel small molecule inhibitor, JP-153, effectively blocked this sensing mechanism in mouse models. These findings establish anti-durotactic therapy as a promising new strategy for treating fibrotic diseases and preventing the progression of metastatic tumors.

References:

• Al-Hilal T A, Chrysovergi M A, Grasberger P E, et al. Durotaxis is a driver and potential therapeutic target in lung fibrosis and metastatic pancreatic cancer[J]. Nature cell biology, 2025, 27(9): 1543-1554.