| dc.description.abstract | Stiffness regulation within the tumour microenvironment plays a pivotal role in tumorigenesis. In this context, integrin α11β1 is a collagen receptor expressed on cancer-associated fibroblasts (CAFs) involved in matrix reorganization. Integrin α11 expression is often upregulated in the stroma of desmoplastic cancers, where integrin α11 can promote tumour progression. The present study aimed at understanding how matrix stiffness regulates integrin α11 expression in fibroblasts. For this purpose, we took advantage of polyacrylamide hydrogels functionalized with matrix ligands of varying stiffness. Surprisingly, BJ fibroblasts and lung CAFs seeded on soft collagen matrices displayed higher integrin α11 expression compared to cells seeded on stiff matrices. Moreover, we found that integrin α11 expression was controlled at the transcriptional level in a collagen I-dependent manner. Our data furthermore suggests that the TGF-β, FAK and Erk signalling pathways are involved in the stiffness-dependent modulation of integrin α11 expression. Altogether, these results highlight a novel regulation of integrin α11 expression, which contributes to our understanding of its role in tissue and tumour fibrosis. | |
