Wnt/beta-catenin and MAPK signaling: allies and enemies in different battlefields

D. Guardavaccaro, H. Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Two papers published in Science Signaling reveal extensive crosstalk between Wnt/beta-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/beta-catenin and MAPK signaling depends on the specific cellular context. Indeed, in melanoma, hyperactivated MAPK signaling down-regulates the Wnt/beta-catenin signal transduction cascade, thereby establishing a negative crosstalk between the two signaling pathways. In contrast, in colorectal cancer, stimulation of the Wnt/beta-catenin pathway leads to activation of the MAPK pathway through Ras stabilization, representing an example of positive crosstalk. Moreover, activation of Wnt/beta-catenin signaling has context-dependent functions that trigger opposing effects on tumor growth. In melanoma, aberrant activation of Wnt/beta-catenin signaling may have anti-oncogenic functions by promoting programmed cell death; by contrast, in the intestine, Wnt/beta-catenin signaling drives malignant transformation. Thus, there is no single correct way to target the Wnt/beta-catenin pathway for all cancers.
Original languageEnglish
Pages (from-to)15
JournalScience Signaling
Volume5
Issue number219
DOIs
Publication statusPublished - 2012

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