Integrin α9β1 promotes malignant tumor growth and metastasis by potentiating epithelial-mesenchymal transition

S. K. Gupta, S. Oommen, M. C. Aubry, B. P. Williams, N. E. Vlahakis

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The integrin α9β1 binds a number of extracellular matrix components to mediate cell adhesion, migration and tissue invasion. Although expressed in a variety of normal human cells including endothelium, it is also expressed in cancer cells. We have previously shown that α9β1 binds VEGF-A to facilitate angiogenesis, an important component of the tumor microenvironment. As α9β1 induces accelerated cancer cell migration, we wished to determine what role it played in cancer growth and metastasis. In this study, we show that α9β1 expression induces molecular changes consistent with epithelial-mesenchymal transition. In addition, we found that α9β1 forms a tri-partite protein complex with β-catenin and E-cadherin, which dissociates following integrin activation and subsequent src and β-catenin phosphorylation. These findings were consistent in cells in which: α9β1 was exogenously over-expressed, or when its expression was suppressed in cancer cells endogenously expressing α9β1. These in vitro results are biologically significant as α9β1-expressing cancer cells induce greater tumor growth and metastases in mice as compared to the cells without α9β1 expression or when integrin expression is suppressed. Furthermore, integrin α9β1 is expressed in primary human small cell lung cancer and patients having a high expression of α9β1 demonstrated significantly worse long-term survival compared with patients with low α9β1 expression. These findings highlight a novel mechanism of integrin α9β1 function in human cancer.

Original languageEnglish (US)
Pages (from-to)141-150
Number of pages10
JournalOncogene
Volume32
Issue number2
DOIs
StatePublished - Jan 10 2013

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Epithelial-Mesenchymal Transition
Integrins
Neoplasm Metastasis
Growth
Neoplasms
Catenins
Cell Movement
Tumor Microenvironment
Small Cell Lung Carcinoma
Cadherins
Cell Adhesion
Vascular Endothelial Growth Factor A
Endothelium
Extracellular Matrix
Phosphorylation
Survival

Keywords

  • α9β1 integrin
  • cell migration
  • EMT
  • lung cancer
  • metastasis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Integrin α9β1 promotes malignant tumor growth and metastasis by potentiating epithelial-mesenchymal transition. / Gupta, S. K.; Oommen, S.; Aubry, M. C.; Williams, B. P.; Vlahakis, N. E.

In: Oncogene, Vol. 32, No. 2, 10.01.2013, p. 141-150.

Research output: Contribution to journalArticle

Gupta, S. K. ; Oommen, S. ; Aubry, M. C. ; Williams, B. P. ; Vlahakis, N. E. / Integrin α9β1 promotes malignant tumor growth and metastasis by potentiating epithelial-mesenchymal transition. In: Oncogene. 2013 ; Vol. 32, No. 2. pp. 141-150.
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