Integrin α11 cytoplasmic tail is required for FAK activation to initiate 3D cell invasion and ERK-mediated cell proliferation

Sci Rep. 2019 Oct 25;9(1):15283. doi: 10.1038/s41598-019-51689-6.


Integrin α11β1 is a collagen-binding integrin, which is receiving increasing attention in the context of wound healing and fibrosis. Although α11β1 integrin displays similar collagen specificity to α2β1 integrin, both integrins have distinct in vivo functions. In this context, the contribution of α11 subunit cytoplasmic tail interactions to diverse molecular signals and biological functions is largely unknown. In the current study, we have deleted the α11 cytoplasmic tail and studied the effect of this deletion on α11 integrin function. Compared to wild-type cells, C2C12 cells expressing tail-less α11 attached normally to collagen I, but formed fewer focal contacts. α11-tail-less cells furthermore displayed a reduced capacity to invade and reorganize a 3D collagen matrix and to proliferate. Analysis of cell signaling showed that FAK and ERK phosphorylation was reduced in cells expressing tail-less α11. Inhibition of ERK and FAK activation decreased α11-mediated cell proliferation, whereas α11-mediated cell invasion was FAK-dependent and occurred independently of ERK signaling. In summary, our data demonstrate that the integrin α11 cytoplasmic tail plays a central role in α11 integrin-specific functions, including FAK-dependent ERK activation to promote cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Collagen Type I / metabolism
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • HEK293 Cells
  • Humans
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / metabolism*
  • Mice
  • Phosphorylation
  • Signal Transduction / physiology


  • Collagen Type I
  • ITGA11 protein, human
  • Integrin alpha Chains
  • Focal Adhesion Protein-Tyrosine Kinases
  • Extracellular Signal-Regulated MAP Kinases