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Integrin-Mediated TGFβ Activation Modulates the Tumour Microenvironment

Centre for Tumour Biology, Barts Cancer Institute, Cancer Research UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
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Cancers 2019, 11(9), 1221; https://doi.org/10.3390/cancers11091221
Received: 19 July 2019 / Revised: 12 August 2019 / Accepted: 15 August 2019 / Published: 21 August 2019
(This article belongs to the Special Issue The Role of Integrins in Cancer)
TGFβ (transforming growth factor-beta) is a pleotropic cytokine with contrasting effects in cancer. In normal tissue and early tumours, TGFβ acts as a tumour suppressor, limiting proliferation and inducing apoptosis. However, these effects are eventually abrogated by the loss or inactivation of downstream signalling within the TGFβ pathway, and in established tumours, TGFβ then acts as a tumour promotor through multiple mechanisms including inducing epithelial-to-mesenchymal transition (EMT), promoting formation of cancer-associated fibroblasts (CAFs) and increasing angiogenesis. TGFβ is secrereted as a large latent complex and is embedded in the extracellular matrix or held on the surface of cells and must be activated before mediating its multiple functions. Thus, whilst TGFβ is abundant in the tumour microenvironment (TME), its functionality is regulated by local activation. The αv-integrins are major activators of latent-TGFβ. The potential benefits of manipulating the immune TME have been highlighted by the clinical success of immune-checkpoint inhibitors in a number of solid tumour types. TGFβ is a potent suppressor of T-cell-mediated immune surveillance and a key cause of resistance to checkpoint inhibitors. Therefore, as certain integrins locally activate TGFβ, they are likely to have a role in the immunosuppressive TME, although this remains to be confirmed. In this review, we discussed the role of TGFβ in cancer, the role of integrins in activating TGFβ in the TME, and the potential benefits of targeting integrins to augment immunotherapies. View Full-Text
Keywords: integrins; TGFβ; αvβ6; tumour microenvironment integrins; TGFβ; αvβ6; tumour microenvironment
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MDPI and ACS Style

Brown, N.F.; Marshall, J.F. Integrin-Mediated TGFβ Activation Modulates the Tumour Microenvironment. Cancers 2019, 11, 1221. https://doi.org/10.3390/cancers11091221

AMA Style

Brown NF, Marshall JF. Integrin-Mediated TGFβ Activation Modulates the Tumour Microenvironment. Cancers. 2019; 11(9):1221. https://doi.org/10.3390/cancers11091221

Chicago/Turabian Style

Brown, Nicholas F.; Marshall, John F. 2019. "Integrin-Mediated TGFβ Activation Modulates the Tumour Microenvironment" Cancers 11, no. 9: 1221. https://doi.org/10.3390/cancers11091221

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