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

Jonathan Cooper, Filippo G. Giancotti

Research output: Contribution to journalReview articlepeer-review

464 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)347-367
Number of pages21
JournalCancer cell
Volume35
Issue number3
DOIs
StatePublished - Mar 18 2019

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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