Durotaxis—cell migration along stiffness gradients—is implicated in development, repair, and disease, though its in vivo role remains unclear. We show that durotaxis actively drives disease progression in mouse models of lung fibrosis (IPF) and metastatic pancreatic cancer. In fibrosis, it guides fibroblasts to injury sites, triggering their activation into scar-forming myofibroblasts. In cancer, tumor stiffening promotes cancer cell durotaxis and metastasis. This process is mediated by FAK–paxillin interaction, linking mechanical cues to YAP-driven transcription. Disrupting this interaction via a FAK-FATL994E knock-in or the small molecule JP-153 blocks durotaxis and reduces disease severity. Our results identify durotaxis as a key in vivo disease mechanism and a target for fibrosis and cancer therapy.
Read the full publication in Nature Cell Biology: https://doi.org/10.1038/s41556-025-01697-8 and
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