AV Integrins and TGF-β-induced EMT: a Circle of Regulation

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2011 Sep 3

PMID 21883891

Citations 95

Authors

Fahmy A Mamuya

Melinda K Duncan

Affiliations

Soon will be listed here.

Abstract

Transforming growth factor-β (TGF-β) has roles in embryonic development, the prevention of inappropriate inflammation and tumour suppression. However, TGF-β signalling also regulates pathological epithelial-to-mesenchymal transition (EMT), inducing or progressing a number of diseases ranging from inflammatory disorders, to fibrosis and cancer. However, TGF-β signalling does not proceed linearly but rather induces a complex network of cascades that mutually influence each other and cross-talk with other pathways to successfully induce EMT. Particularly, there is substantial evidence for cross-talk between αV integrins and TGF-β during EMT, and anti-integrin therapeutics are under development as treatments for TGF-β-related disorders. However, TGF-β's complex signalling network makes the development of therapeutics to block TGF-β-mediated pathology challenging. Moreover, despite our current understanding of integrins and TGF-β function during EMT, the precise mechanism of their role during physiological versus pathological EMT is not fully understood. This review focuses on the circle of regulation between αV integrin and TGF-β signalling during TGF-β induced EMT, which pose as a significant driver to many known TGF-β-mediated disorders.

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References

Chernousov M, Carey D . alphaVbeta8 integrin is a Schwann cell receptor for fibrin. Exp Cell Res. 2003; 291(2):514-24. DOI: 10.1016/s0014-4827(03)00409-9. View

Mu D, Cambier S, Fjellbirkeland L, Baron J, Munger J, Kawakatsu H . The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1. J Cell Biol. 2002; 157(3):493-507. PMC: 2173277. DOI: 10.1083/jcb.200109100. View

Annes J, Munger J, Rifkin D . Making sense of latent TGFbeta activation. J Cell Sci. 2002; 116(Pt 2):217-24. DOI: 10.1242/jcs.00229. View

Galliher A, Schiemann W . Beta3 integrin and Src facilitate transforming growth factor-beta mediated induction of epithelial-mesenchymal transition in mammary epithelial cells. Breast Cancer Res. 2006; 8(4):R42. PMC: 1779461. DOI: 10.1186/bcr1524. View

Ruoslahti E . RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol. 1996; 12:697-715. DOI: 10.1146/annurev.cellbio.12.1.697. View

Derynck R, Zhang Y . Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003; 425(6958):577-84. DOI: 10.1038/nature02006. View

Schoenwaelder S, Burridge K . Bidirectional signaling between the cytoskeleton and integrins. Curr Opin Cell Biol. 1999; 11(2):274-86. DOI: 10.1016/s0955-0674(99)80037-4. View

Anthis N, Campbell I . The tail of integrin activation. Trends Biochem Sci. 2011; 36(4):191-8. PMC: 3078336. DOI: 10.1016/j.tibs.2010.11.002. View

Yilmaz M, Christofori G . EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009; 28(1-2):15-33. DOI: 10.1007/s10555-008-9169-0. View

10.

Platten M, Wick W, Aulwurm S, Dichgans J, Weller M . Transforming growth factors beta(1) (TGF-beta(1)) and TGF-beta(2) promote glioma cell migration via Up-regulation of alpha(V)beta(3) integrin expression. Biochem Biophys Res Commun. 2000; 268(2):607-11. DOI: 10.1006/bbrc.2000.2176. View

11.

Li Y, Dai C, Wu C, Liu Y . PINCH-1 promotes tubular epithelial-to-mesenchymal transition by interacting with integrin-linked kinase. J Am Soc Nephrol. 2007; 18(9):2534-43. DOI: 10.1681/ASN.2007030315. View

12.

Souchelnytskyi S, Ronnstrand L, Heldin C, Ten Dijke P . Phosphorylation of Smad signaling proteins by receptor serine/threonine kinases. Methods Mol Biol. 2000; 124:107-20. DOI: 10.1385/1-59259-059-4:107. View

13.

Honda E, Yoshida K, Munakata H . Transforming growth factor-beta upregulates the expression of integrin and related proteins in MRC-5 human myofibroblasts. Tohoku J Exp Med. 2010; 220(4):319-27. DOI: 10.1620/tjem.220.319. View

14.

Bianchi A, Gervasi M, Bakin A . Role of β5-integrin in epithelial-mesenchymal transition in response to TGF-β. Cell Cycle. 2010; 9(8):1647-59. DOI: 10.4161/cc.9.8.11517. View

15.

Oharazawa H, Ibaraki N, Ohara K, Reddy V . Inhibitory effects of Arg-Gly-Asp (RGD) peptide on cell attachment and migration in a human lens epithelial cell line. Ophthalmic Res. 2005; 37(4):191-6. DOI: 10.1159/000086595. View

16.

Peinado H, Olmeda D, Cano A . Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007; 7(6):415-28. DOI: 10.1038/nrc2131. View

17.

Zeisberg M, Bottiglio C, Kumar N, Maeshima Y, Strutz F, Muller G . Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models. Am J Physiol Renal Physiol. 2003; 285(6):F1060-7. DOI: 10.1152/ajprenal.00191.2002. View

18.

DAndrea L, Del Gatto A, Pedone C, Benedetti E . Peptide-based molecules in angiogenesis. Chem Biol Drug Des. 2006; 67(2):115-26. DOI: 10.1111/j.1747-0285.2006.00356.x. View

19.

Breuss J, Gallo J, DeLisser H, Klimanskaya I, Folkesson H, Pittet J . Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. J Cell Sci. 1995; 108 ( Pt 6):2241-51. DOI: 10.1242/jcs.108.6.2241. View

20.

Cambier S, Gline S, Mu D, Collins R, Araya J, Dolganov G . Integrin alpha(v)beta8-mediated activation of transforming growth factor-beta by perivascular astrocytes: an angiogenic control switch. Am J Pathol. 2005; 166(6):1883-94. PMC: 1602409. DOI: 10.1016/s0002-9440(10)62497-2. View