title: Wnt/β-catenin and MAPK signaling: allies and enemies in different battlefields.
abstract: Two papers published in Science Signaling reveal extensive crosstalk between Wnt/β-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/β-catenin and MAPK signaling depends on the specific cellular context. Indeed, in melanoma, hyperactivated MAPK signaling down-regulates the Wnt/β-catenin signal transduction cascade, thereby establishing a negative crosstalk between the two signaling pathways. In contrast, in colorectal cancer, stimulation of the Wnt/β-catenin pathway leads to activation of the MAPK pathway through Ras stabilization, representing an example of positive crosstalk. Moreover, activation of Wnt/β-catenin signaling has context-dependent functions that trigger opposing effects on tumor growth. In melanoma, aberrant activation of Wnt/β-catenin signaling may have anti-oncogenic functions by promoting programmed cell death; by contrast, in the intestine, Wnt/β-catenin signaling drives malignant transformation. Thus, there is no single correct way to target the Wnt/β-catenin pathway for all cancers.
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
authors.forename: Daniele
authors.initials: D
authors.lastname: Guardavaccaro
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D060466:Axin Protein / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D060466:Axin Protein; D051153:Wnt Proteins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D048493:Proto-Oncogene Proteins B-raf; D038362:Glycogen Synthase Kinase 3; D018631:ras Proteins