Transforming growth factor-β in tumour development

Charles B Trelford; Lina Dagnino; Gianni M Di Guglielmo

doi:10.3389/fmolb.2022.991612

Transforming growth factor-β in tumour development

Front Mol Biosci. 2022 Oct 4:9:991612. doi: 10.3389/fmolb.2022.991612. eCollection 2022.

Authors

Charles B Trelford¹, Lina Dagnino^{1

2}, Gianni M Di Guglielmo¹

Affiliations

¹ Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
² Department of Oncology, Children's Health Research Institute and Lawson Health Research Institute, London, ON, Canada.

Abstract

Transforming growth factor-β (TGFβ) is a ubiquitous cytokine essential for embryonic development and postnatal tissue homeostasis. TGFβ signalling regulates several biological processes including cell growth, proliferation, apoptosis, immune function, and tissue repair following injury. Aberrant TGFβ signalling has been implicated in tumour progression and metastasis. Tumour cells, in conjunction with their microenvironment, may augment tumourigenesis using TGFβ to induce epithelial-mesenchymal transition, angiogenesis, lymphangiogenesis, immune suppression, and autophagy. Therapies that target TGFβ synthesis, TGFβ-TGFβ receptor complexes or TGFβ receptor kinase activity have proven successful in tissue culture and in animal models, yet, due to limited understanding of TGFβ biology, the outcomes of clinical trials are poor. Here, we review TGFβ signalling pathways, the biology of TGFβ during tumourigenesis, and how protein quality control pathways contribute to the tumour-promoting outcomes of TGFβ signalling.

Keywords: Smad; autophagy; epithelial-mesenchymal transition (EMT); protein 62/sequestosome 1 (p62/SQSTM1); receptor trafficking; transforming growth factor-b (TGFb).

Publication types

Review