Alpha2beta1 integrin in cancer development and chemoresistance

Semin Cancer Biol. 2015 Dec:35:145-53. doi: 10.1016/j.semcancer.2015.08.004. Epub 2015 Aug 20.

Abstract

Extracellular matrix, via its receptors the integrins, has emerged as a crucial factor in cancer development. The α2β1 integrin is a major collagen receptor that is widely expressed and known to promote cell migration and control tissue homeostasis. Growing evidence suggests that it can be a key pathway in cancer. Recent studies have shown that α2β1 integrin is a regulator of cancer metastasis either by promoting or inhibiting the dissemination process of cancer cells. The α2β1 integrin signaling can also enhance tumor angiogenesis. Emerging evidence supports a role for α2β1 integrin in cancer chemoresistance especially in hematological malignancies originating from the T cell lineage. In addition, α2β1 integrin has been associated with cancer stem cells. In this review, we will discuss the complex role of α2β1 integrin in these processes. Collagen is a major matrix protein of the tumor microenvironment and thus, understanding how α2β1 integrin regulates cancer pathogenesis is likely to lead to new therapeutic approaches and agents for cancer treatment.

Keywords: Alpha2beta1 integrin; Collagen; Hematological malignancies; Metastasis; chemoresistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • Collagen / metabolism
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics*
  • Extracellular Matrix / metabolism
  • Humans
  • Integrin alpha2beta1 / antagonists & inhibitors
  • Integrin alpha2beta1 / genetics*
  • Integrin alpha2beta1 / metabolism*
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplastic Stem Cells / metabolism
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Signal Transduction

Substances

  • Integrin alpha2beta1
  • Collagen