1Microenvironmentrigiditymodulatesresponsestothe.PDF

Microenvironment rigidity modulates responses to the HER2 receptor tyrosine kinase inhibitor lapatinib via YAP and TAZ transcription factors a,b a,c d e ChunHan Lin , Fanny A Pelissier , Hui Zhang , Jon Lakins ,Valerie M. e d a# Weaver , Catherine Park , and Mark A LaBarge Affiliations: a. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA b. Program in Comparative Biochemistry, University of California Berkeley, Berkeley, CA c. Department of Biomedicine, University of Bergen, Bergen, Norway d. Department of Radiation Oncology, University of California San Francisco, San Francisco, CA e. Center for Bioengineering, Tissue Regeneration, Department of Surgery, UCSF, San Francisco, USA #. Address correspondence to: Mark LaBarge (malabarge@) Abbreviations used: HER2: Human epidermal growth factor receptor 2 HER3: Human epidermal growth factor receptor 3 EGFR: Epidermal growth factor receptor HGF: Hepatocyte growth factor 1 Supplemental Material can be found at: /content/suppl/2015/08/31/mbc.E15-07-0456v1.DC1.html MET: Hepatocyte growth factor receptor TCP: Tissue culture plastic PA: Polyacrylamide IPTG: Isopropyl β-D-1-thiogalactopyranoside AREG: Amphiregulin RTK: Receptor tyrosine kinase AUC: Area under curve Abstract Stiffness is a biophysical property of the extracellular matrix that modulates cellular functions, including proliferation, invasion, and differentiation, and it also may impact therapeutic responses. Therapeutic durability in cancer treatments remains a problem both for chemotherapies and pathway-targeted drugs, but the reasons for this are not well understood. Tumor progression is accompanied by changes in the biophysical properties of the tissue