Widespread Repression of Gene Expression in Cancer by a Wnt/?-Catenin/MAPK Pathway

Abstract Aberrant Wnt signaling drives a number of cancers through regulation diverse downstream pathways. Wnt/?-catenin achieves this in part by increasing the expression proto-oncogenes such as MYC and cyclins. However, global assessment Wnt-regulated transcriptome vivo genetically distinct demonstrates that suppresses many genes it activates. In study, we examined set are upregulated upon inhibition Wnt-addicted pancreatic colorectal cancer models. Decreasing led to marked increase gene activating ERK JNK; these changes could be mitigated concurrent MEK. These findings demonstrate increased represses MAPK activity, preventing RAS-mediated senescence while allowing cells proliferate. results shift paradigm from primarily an activator transcription more nuanced view where both widespread repression activation. Significance: show causes via signaling, thus fine tuning RAS-MAPK pathway optimize proliferation cancer.