TGFβ: the molecular Jekyll and Hyde of cancer

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Abstract
TGFβ signalling is tumour suppressive in epithelial cells, whereas it can promote invasion and metastasis during the later stages of carcinoma progression. During tumour progression, tumour cells frequently lose the growth-inhibitory response to TGFβ, and this is associated with an increased expression of TGFβ in the microenvironment. TGFβ-mediated regulation in the tumour microenvironment can be attributed to many factors, including those that involve cell-autonomous signalling, stromal–epithelial interactions, inflammation, immune evasion and angiogenesis. Cell-autonomous TGFβ signalling can cause epithelial–mesenchymal transitions (EMT) in carcinoma cells, which increase invasion and metastasis. Conversely, the abrogation of carcinoma-cell-autonomous TGFβ signalling can increase metastasis in the apparent absence of EMT. Together, the cell-type-dependent and context-dependent effects of TGFβ signalling contribute to the regulation of tumour initiation, progression and metastasis. Despite the complex nature of TGFβ-mediated regulatory signalling in the tumour microenvironment, many aspects of signalling through this pathway have been targeted for therapeutic intervention using systemic and cell-specific strategies, with some indications of efficacy.