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

Moses Musiime, Pugazendhi Murugan Erusappan, Edna Cukierman, Joan Chang, Anders Molven, Cédric Zeltz, Donald Gullberg

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)144-161
Number of pages18
JournalMatrix Biology
Volume134
Early online dateSep 13 2024
DOIs
StatePublished - Dec 2024

Keywords

  • Cancer-associated fibroblast
  • Collagen assembly
  • Fibrillar adhesions
  • Fibrosis
  • Integrin
  • Collagen Type I/metabolism
  • Extracellular Matrix/metabolism
  • Tensins/metabolism
  • Cancer-Associated Fibroblasts/metabolism
  • Humans
  • Receptors, Collagen/metabolism
  • Integrins/metabolism
  • Pancreatic Neoplasms/metabolism
  • Cell Adhesion
  • Integrin alpha5beta1/metabolism
  • Carcinoma, Pancreatic Ductal/metabolism
  • Fibroblasts/metabolism
  • Cell Line, Tumor

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