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

TY - JOUR

T1 - Wnt/beta-catenin and MAPK signaling: allies and enemies in different battlefields

AU - Guardavaccaro, D.

AU - Clevers, H.

N1 - Reporting year: 2012

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1126/scisignal.2002921

DO - 10.1126/scisignal.2002921

M3 - Article

SN - 1937-9145

VL - 5

SP - 15

JO - Science Signaling

JF - Science Signaling

IS - 219

ER -