The role of integrins in TGFβ activation in the tumour stroma
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- 作者：Zareen Khan ; John F. Marshall
- 关键词：TGFβ ; Integrin ; αvβ1 ; αvβ3 ; αvβ5 ; αvβ6 ; αvβ8 ; Tumour stroma ; Tumour microenvironment
- 刊名：Cell and Tissue Research
- 出版年：2016
- 出版时间：September 2016
- 年：2016
- 卷：365
- 期：3
- 页码：657-673
- 全文大小：1,135 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Human Genetics
Proteomics
Molecular Medicine - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-0878
- 卷排序：365
文摘
TGFβ1 is the most pleiotropic of all known cytokines and thus, to avoid uncontrolled TGFβ-activated processes, its activity is tightly regulated. Studies in fibrosis have led to the discovery that αv integrins are the major regulators of the local activation of latent TGFβ in our tissues. Since all cells can express one or more types of αv integrins, this raises the possibility that, in the complex milieu of a developing cancer, multiple cell types including both cancer cells and stromal cells activate TGFβ. In normal tissues, TGFβ1 is a tumour suppressor through its ability to suppress epithelial cell division, whereas in cancer, in which tumour cells develop genetic escape mechanisms to become resistant to TGFβ growth suppression, TGFβ signalling creates a tumour-permissive environment by activating fibroblast-to-myofibroblast transition, by promoting angiogenesis, by suppressing immune cell populations and by promoting the secretion of both matrix proteins and proteases. In addition, TGFβ drives epithelial-to-mesenchymal transition (EMT) increasing the potential for metastasis. Since αv integrins activate TGFβ, they almost certainly drive TGFβ-dependent cancer progression. In this review, we discuss the data that are helping to develop this hypothesis and describe the evidence that αv integrins regulate the TGFβ promotion of cancer.