Clinical significance of the integrin α6β4 in human malignancies

Rachel L. Stewart, Kathleen L. O'Connor

Research output: Contribution to journalReview articlepeer-review

117 Scopus citations

Abstract

Integrin α6β4 is a cellular adhesion molecule that binds to laminins in the extracellular matrix and nucleates the formation of hemidesmosomes. During carcinoma progression, integrin α6β4 is released from hemidesmosomes, where it can then signal to facilitate multiple aspects of tumor progression including sustaining proliferative signaling, tumor invasion and metastasis, evasion of apoptosis, and stimulation of angiogenesis. The integrin achieves these ends by cooperating with growth factor receptors including EGFR, ErbB-2, and c-Met to amplify downstream pathways such as PI3K, AKT, MAPK, and the Rho family small GTPases. Furthermore, it dramatically alters the transcriptome toward a more invasive phenotype by controlling promoter DNA demethylation of invasion and metastasis-associated proteins, such as S100A4 and autotaxin, and upregulates and activates key tumor-promoting transcription factors such as the NFATs and NF-κB. Expression of integrin α6β4 has been studied in many human malignancies where its overexpression is associated with aggressive behavior and a poor prognosis. This review provides an assessment of integrin α6β4 expression patterns and their prognostic significance in human malignancies, and describes key signaling functions of integrin α6β4 that contribute to tumor progression.

Original languageEnglish
Pages (from-to)976-986
Number of pages11
JournalLaboratory Investigation
Volume95
Issue number9
DOIs
StatePublished - Sep 28 2015

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants T32 CA160003 (to RLS) and R01 CA109136 (to KLO).

Publisher Copyright:
© 2015 USCAP, Inc.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Clinical significance of the integrin α6β4 in human malignancies'. Together they form a unique fingerprint.

Cite this