Transforming growth factor-β, MAPK and Wnt signaling interactions in colorectal cancer

•TGFβ promotes tumor growth during cancer through Smad-independent mechanisms.•TGFβ does not have single signaling signature.•TGFβ and its receptors participate in crosstalk with various MAPK pathways.•Wnt and TGFβ together regulate genes that are involved in the EMT.•Genetic alterations to TGFβ signalling further add to the complexity of TGFβ crosstalk.

In non-cancerous cells, transforming growth factor-β (TGFβ) regulates cellular responses primarily through Smad signaling. However, during cancer progression (including colorectal) TGFβ promotes tumoral growth via Smad-independent mechanisms and is involved in crosstalk with various pathways like the mitogen-activated protein kinases (MAPK) and Wnt. Crosstalk between these pathways following activation by TGFβ and subsequent downstream signaling activity can be referred to as a crosstalk signaling signature. This review highlights the progress in understanding TGFβ signaling crosstalk involving various MAPK pathway members (e.g., extracellular signal-regulated kinase (Erk) 1/2, Ras, c-Jun N-terminal kinases (JNK) and p38) and the Wnt signaling pathway.

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