Integrin α6β4 in Colorectal Cancer: Expression, Regulation, Functional Alterations and Use as a Biomarker

Abstract

Integrin α6β4 is one of the main laminin receptors and is primarily expressed by epithelial cells as an active component of hemidesmosomes. In this article, after a brief summary about integrins in the gut epithelium in general, I review the knowledge and clinical potential of this receptor in human colorectal cancer (CRC) cells. Most CRC cells overexpress both α6 and β4 subunits, in situ in primary tumours as well as in established CRC cell lines. The mechanisms that lead to overexpression have not yet been elucidated but clearly involve specific transcription factors such as MYC. From a functional point of view, one key element affecting CRC cell behaviour is the relocalization of α6β4 to the actin cytoskeleton, favouring a more migratory and anoikis-resistant phenotype. Another major element is its expression under various molecular forms that have the distinct ability to interact with ligands (α6β4 ± ctd) or to promote pro- or anti-proliferative properties (α6Aβ4 vs. α6Bβ4). The integrin α6β4 is thus involved in most steps susceptible to participation with CRC progression. The potential clinical significance of this integrin has begun to be investigated and recent studies have shown that ITGA6 and ITGB4 can be useful biomarkers for CRC early detection in a non-invasive assay and as a prognostic factor, respectively.