Fibroblast integrin α11β1 is a collagen assembly receptor in mechanoregulated fibrillar adhesions.

Solid epithelial cancers with significant desmoplasia are characterized by an excessive deposition of collagen-based matrix, which often supports tumor progression. However, the mechanism of how collagen receptors mediate collagen fibrillogenesis still remains mostly unclear. We show that the collagen-binding integrin α11β1 can co-localize with tensin-1 and deposited collagen I in human pancreatic ductal adenocarcinoma (PDAC) stroma. In addition to the canonical fibrillar adhesion integrin α5β1 expressed by human PDAC cancer-associated fibroblasts (CAFs), tensin-1-positive fibrillar adhesions contained α11β1 but lacked α1β1 and α2β1. CAFs lacking α5β1 expression displayed mechanoregulated and tensin-1 dependent α11β1 fibrillar adhesions, suggesting independent roles of the two integrins with regards to fibrillar adhesions-based de novo fibrillogenesis. Further, we demonstrate that cell surface-associated collagen I assembly necessitated α11β1, but not α5β1 expression. In summary, α11β1 integrin is a novel component of fibrillar adhesions, which is strategically positioned to mediate de novo collagen fibrillogenesis at the cell surface under pro-fibrotic conditions.