Integrin-TGF-beta crosstalk in fibrosis, cancer and wound healing.
Accumulating evidence indicates that there is extensive crosstalk between integrins and TGF-beta signalling. TGF-beta affects integrin-mediated cell adhesion and migration by regulating the expression of integrins, their ligands and integrin-associated proteins. Conversely, several integrins directly control TGF-beta activation. In addition, a number of integrins can interfere with both Smad-dependent and Smad-independent TGF-beta signalling in different ways, including the regulation of the expression of TGF-beta signalling pathway components, the physical association of integrins with TGF-beta receptors and the modulation of downstream effectors. Reciprocal TGF-beta-integrin signalling is implicated in normal physiology, as well as in a variety of pathological processes including systemic sclerosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and cancer; thus, integrins could provide attractive therapeutic targets to interfere with TGF-beta signalling in these processes.
Margadant
Coert
C
Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Sonnenberg
Arnoud
A
D000818:Animals; D018450:Disease Progression; D005355:Fibrosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
D016023:Integrins; D016212:Transforming Growth Factor beta