The biological and biomechanical role of transglutaminase-2 in the tumour microenvironment

TEMPEST, Robert, GUARNERIO, Sonia, MAANI, Rawan, COOPER, Jamie and PEAKE, Nicholas (2021). The biological and biomechanical role of transglutaminase-2 in the tumour microenvironment. Cancers, 13 (11).

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Transglutaminase-2 (TG2) is the most highly and ubiquitously expressed member of the transglutaminase enzyme family and is primarily involved in protein cross-linking. TG2 has been implicated in the development and progression of numerous cancers, with a direct role in multiple cellular processes and pathways linked to apoptosis, chemoresistance, epithelial-mesenchymal transition, and stem cell phenotype. The tumour microenvironment (TME) is critical in the formation, progression, and eventual metastasis of cancer, and increasing evidence points to a role for TG2 in matrix remodelling, modulation of biomechanical properties, cell adhesion, motility, and invasion. There is growing interest in targeting the TME therapeutically in response to advances in the understanding of its critical role in disease progression, and a number of approaches targeting biophysical properties and biomechanical signalling are beginning to show clinical promise. In this review we aim to highlight the wide array of processes in which TG2 influences the TME, focussing on its potential role in the dynamic tissue remodelling and biomechanical events increasingly linked to invasive and aggressive behaviour. Drug development efforts have yielded a range of TG2 inhibitors, and ongoing clinical trials may inform strategies for targeting the biomolecular and biomechanical function of TG2 in the TME.

Item Type: Article
Additional Information: ** From MDPI via Jisc Publications Router ** Licence for this article: **Journal IDs: eissn 2072-6694 **History: published 03-06-2021; accepted 27-05-2021
Uncontrolled Keywords: transglutaminase, biomechanics, extracellular matrix, tumour microenvironment
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SWORD Depositor: Colin Knott
Depositing User: Colin Knott
Date Deposited: 07 Jun 2021 11:16
Last Modified: 07 Jun 2021 11:30

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