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Sci. Signal., 10 April 2012
Vol. 5, Issue 219, p. pe15
[DOI: 10.1126/scisignal.2002921]


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

Daniele Guardavaccaro and Hans Clevers*

Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, Netherlands.

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.

* Corresponding author. E-mail: h.clevers{at}

Citation: D. Guardavaccaro, H. Clevers, Wnt/β-Catenin and MAPK Signaling: Allies and Enemies in Different Battlefields. Sci. Signal. 5, pe15 (2012).

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E. Ferreira, R. M. Porter, N. Wehling, R. P. O'Sullivan, F. Liu, A. Boskey, D. M. Estok, M. B. Harris, M. S. Vrahas, C. H. Evans, et al. (2013)
J. Biol. Chem. 288, 29494-29505
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