Wnt/ -Catenin and MAPK Signaling: Allies and Enemies in Different Battlefields

Two papers published in Science Signaling reveal extensive crosstalk between Wnt/-catenin and mitogen-activated protein kinase (MAPK) signaling in cancer. Although both studies describe previously unknown links between these two signaling pathways, the relationship between Wnt/-catenin and MAPK signaling depends on the specific cellular context. Indeed, in melanoma, hyperactivated MAPK signaling down-regulates the Wnt/-catenin signal transduction cascade, thereby establishing a negative crosstalk between the two signaling pathways. In contrast, in colorectal cancer, stimulation of the Wnt/-catenin pathway leads to activation of the MAPK pathway through Ras stabilization, representing an example of positive crosstalk. Moreover, activation of Wnt/-catenin signaling has context-dependent functions that trigger opposing effects on tumor growth. In melanoma, aberrant activation of Wnt/-catenin signaling may have anti- oncogenic functions by promoting programmed cell death; by contrast, in the intestine, Wnt/-catenin signaling drives malignant transformation. Thus, there is no single correct way to target the Wnt/-catenin pathway for all cancers.