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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