Advertisement

 

 

β-catenin-independent regulation of Wnt target genes by RoR2 and ATF2/ATF4 in colon cancer cells.

β-catenin-independent regulation of Wnt target genes by RoR2 and ATF2/ATF4 in colon cancer cells.
Author Information (click to view)

Voloshanenko O, Schwartz U, Kranz D, Rauscher B, Linnebacher M, Augustin I, Boutros M,


Voloshanenko O, Schwartz U, Kranz D, Rauscher B, Linnebacher M, Augustin I, Boutros M, (click to view)

Voloshanenko O, Schwartz U, Kranz D, Rauscher B, Linnebacher M, Augustin I, Boutros M,

Advertisement

Scientific reports 2018 02 168(1) 3178 doi 10.1038/s41598-018-20641-5

Abstract

Wnt signaling is an evolutionarily conserved signaling route required for development and homeostasis. While canonical, β-catenin-dependent Wnt signaling is well studied and has been linked to many forms of cancer, much less is known about the role of non-canonical, β-catenin-independent Wnt signaling. Here, we aimed at identifying a β-catenin-independent Wnt target gene signature in order to understand the functional significance of non-canonical signaling in colon cancer cells. Gene expression profiling was performed after silencing of key components of Wnt signaling pathway and an iterative signature algorithm was applied to predict pathway-dependent gene signatures. Independent experiments confirmed several target genes, including PLOD2, HADH, LCOR and REEP1 as non-canonical target genes in various colon cancer cells. Moreover, non-canonical Wnt target genes are regulated via RoR2, Dvl2, ATF2 and ATF4. Furthermore, we show that the ligands Wnt5a/b are upstream regulators of the non-canonical signature and moreover regulate proliferation of cancer cells in a β-catenin-independent manner. Our experiments indicate that colon cancer cells are dependent on both β-catenin-dependent and -independent Wnt signaling routes for growth and proliferation.

Submit a Comment

Your email address will not be published. Required fields are marked *

3 × five =

[ HIDE/SHOW ]