The role of integrins in melanoma: a review

Abstract

Integrins are the major family of cell adhesion receptors in humans and essential for a wide range of normal physiology, including formation and maintenance of tissue structure integrity, cell migration, proliferation, and differentiation. Integrins also play a prominent role in tumor growth and metastasis. Translational research has tried to define the contribution of integrins to the phenotypic aggressiveness of melanoma because such knowledge is clinically useful. For example, differential expression of integrins in primary cutaneous melanoma can be used to distinguish indolent from aggressive, prometastatic melanoma. Recent studies have shown that gene expression-based testing of patient-derived melanoma tissue is feasible, and molecular tests may fully replace interventional surgical methods such as sentinel lymph node biopsies in the future. Because of their central role in mediating invasion and metastasis, integrins are likely to be useful biomarkers. Integrins are also attractive candidate targets for interventional therapy. This article focuses on the role of integrins in melanoma and highlights recent advances in the field of translational research.

Figure 1.

Integrin Structure. (a) Integrins are transmembrane adhesion receptors consisting of an ɑ and β subunit. The mammalian genome encodes for 18 ɑ and eight β subunits. (b) ɑ and β subunits combine to form 24 distinct integrin heterodimers. These can be grouped based on ligand specificity and expression pattern. Some integrins such as the β2 and β7 integrins are only found on white blood cells (highlighted in green). Integrins which bind the tripeptide sequence Arg-Gly-Asp (RGD) which is encountered in extracellular matrix proteins like fibronectin and osteopontin as well as adhesion receptors such as cadherin 17 are highlighted in red. Collagen binding integrins are labeled in blue and laminin binding integrins such as the ɑ6β4 integrin are highlighted in purple.

Figure 2.

Targeting the integrin signaling and exocytosis pathway. Integrin function can be targeted at multiple levels by antibodies or small molecules (shown in red): at the level of the cell surface receptor (1), at the level of the adhesome, i.e. the multiprotein adhesion complex that links the integrin cytoplasmic tail to intracellular actin and contains many signaling proteins such as FAK (2), at the level of protein transcription (3) and at the level of microtubular vesicular transport (4). FAK, focal adhesion kinase; Topo-I, type I topoisomerase inhibitors.