Durotaxis is a driver and potential therapeutic target in lung fibrosis and metastatic pancreatic cancer

@article{al-hilal_durotaxis_2025,
	title = {Durotaxis is a driver and potential therapeutic target in lung fibrosis and metastatic pancreatic cancer},
	volume = {27},
	issn = {1465-7392, 1476-4679},
	url = {Al-Hilal 2025 Nat Cell Biol.pdf},
	doi = {10.1038/s41556-025-01697-8},
	abstract = {Abstract
            
              Durotaxis, cell migration along stiffness gradients, is linked to embryonic development, tissue repair and disease. Despite solid in vitro evidence, its role in vivo remains largely speculative. Here we demonstrate that durotaxis actively drives disease progression in vivo in mouse models of lung fibrosis and metastatic pancreatic cancer. In lung fibrosis, durotaxis directs fibroblast recruitment to sites of injury, where they undergo mechano-activation into scar-forming myofibroblasts. In pancreatic cancer, stiffening of the tumour microenvironment induces durotaxis of cancer cells, promoting metastatic dissemination. Mechanistically, durotaxis is mediated by focal adhesion kinase (FAK)–paxillin interaction, a mechanosensory module that links stiffness cues to transcriptional programmes via YAP signalling. To probe this genetically, we generated a FAK-FAT
              L994E
              knock-in mouse, which disrupts FAK–paxillin binding, blocks durotaxis and attenuates disease severity. Pharmacological inhibition of FAK–paxillin interaction with the small molecule JP-153 mimics these effects. Our findings establish durotaxis as a disease mechanism in vivo and support anti-durotactic therapy as a potential strategy for treating fibrosis and cancer.},
	language = {en},
	number = {9},
	urldate = {2025-09-15},
	journal = {Nature Cell Biology},
	author = {Al-Hilal, Taslim A. and Chrysovergi, Maria-Anna and Grasberger, Paula E. and Liu, Fei and Auernheimer, Vera and Zhou, Yan and Xiao, Zebin and Leon-Duque, Mark Anthony and Santos, Alba and Islam, Tamanna and Ligorio, Matteo and Sicard, Delphine and Probst, Clemens K. and Vrbanac, Vladimir and Reddi, Tejaswini S. and Vincent, Ludovic and Happe, Cassandra and Chaum, Edward and Yates, Charles R. and Daneshvar, Kaveh and Mullen, Allan C. and Ting, David and White, Eric S. and Kalluri, Raghu and Woo, Christina M. and Puré, Ellen and Goldmann, Wolfgang H. and Alonso, Jose Luis and Tager, Andrew M. and Engler, Adam J. and Tschumperlin, Daniel J. and Lagares, David},
	month = sep,
	year = {2025},
	pages = {1543--1554},
}