Integrin α6β4 requires plectin and vimentin for adhesion complex distribution and invasive growth

Lei Qi, Teresa Knifley, Min Chen, Kathleen L. O’Connor

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Integrin α6β4 binds plectin to associate with vimentin; however, the biological function remains unclear. Here, we utilized various integrin β4 mutants and CRISPR-Cas9 editing to investigate this association. Upon laminin binding, integrin α6β4 distinctly distributed peripherally as well as centrally, proximal to the nucleus. Upon fibronectin addition, integrin α6β4 was centrally recruited to large focal adhesions (FAs) and enhanced Fak (also known as PTK2) phosphorylation. Integrin β4 plectin-binding mutants or genetic deletion of plectin inhibited β4 recruitment to FAs and integrin α6β4-enhanced cell spreading, migration and three-dimensional invasive growth. Loss of the β4 signaling domain (but retaining plectin binding) blocked migration and invasiveness but not cell spreading, recruitment to FAs or colony growth. Immunostaining revealed that integrin α6β4 redistributed vimentin perinuclearly, where it colocalized with plectin and FAs. Depletion of vimentin completely blocked integrin β4-enhanced invasive growth, Fak phosphorylation and proliferation in three dimensions but not two dimensions. In summary, we demonstrate the essential roles of plectin and vimentin in promoting an invasive phenotype downstream of integrin α6β4.

Original languageEnglish
Article number258471
JournalJournal of Cell Science
Volume135
Issue number2
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health through National Cancer Institute (R01 CA223164-01 to K.L.O.); by a Markey Women Strong Award through the Markey Cancer Foundation (to K.L.O.). Deposited in PMC for release after 12 months.

Funding Information:
The Markey Cancer Center Biostatistics and Bioinformatics, and Flow Cytometry and Immune Monitoring Shared Resource Facilities, which supplied services for this study, are supported by National Institutes of Health (P30 CA177558). This study was supported by the National Institutes of Health through National Cancer Institute (R01 CA223164-01 to K.L.O.); by a Markey Women Strong Award through the Markey Cancer Foundation (to K.L.O.). Deposited in PMC for release after 12 months.

Funding Information:
The Markey Cancer Center Biostatistics and Bioinformatics, and Flow Cytometry and Immune Monitoring Shared Resource Facilities, which supplied services for this study, are supported by National Institutes of Health (P30 CA177558).

Publisher Copyright:
© 2022. Published by The Company of Biologists Ltd

Keywords

  • Fibrillar adhesions
  • Focal adhesion kinase
  • Focal adhesions
  • Integrin α6β4
  • Triple negative breast cancer
  • Vimentin

ASJC Scopus subject areas

  • Cell Biology

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