Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance

Cancer Cell. 2019 Mar 18;35(3):347-367. doi: 10.1016/j.ccell.2019.01.007.


Integrins mediate cell adhesion and transmit mechanical and chemical signals to the cell interior. Various mechanisms deregulate integrin signaling in cancer, empowering tumor cells with the ability to proliferate without restraint, to invade through tissue boundaries, and to survive in foreign microenvironments. Recent studies have revealed that integrin signaling drives multiple stem cell functions, including tumor initiation, epithelial plasticity, metastatic reactivation, and resistance to oncogene- and immune-targeted therapies. Here, we discuss the mechanisms leading to the deregulation of integrin signaling in cancer and its various consequences. We place emphasis on novel functions, determinants of context dependency, and mechanism-based therapeutic opportunities.

Keywords: FAK signaling; cancer stem cell; extracellular niche; integrins; mechanotransduction; metastasis and invasion; receptor tyrosine kinase; therapeutic resistance; therapeutic targeting of integrins; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Cell Plasticity
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrins / metabolism*
  • Mechanotransduction, Cellular
  • Neoplasms / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Signal Transduction


  • Integrins