Wnt2 complements Wnt/β-catenin signaling in colorectal cancer.

Content Provider	Europe PMC
Author	Jung, Youn-Sang Jun, Sohee Lee, Sun Hye Sharma, Amrish Park, Jae-Il
Copyright Year	2015
Abstract	Wnt2 is implicated in various human cancers. However, it remains unknown how Wnt2 is upregulated in human cancer and contributes to tumorigenesis. Here we found that Wnt2 is highly expressed in colorectal cancer (CRC) cells. In addition to co-expression of Wnt2 with Wnt/β-catenin target genes in CRC, knockdown or knockout of Wnt2 significantly downregulates Wnt/β-catenin target gene expression in CRC cells. Importantly, depletion or ablation of endogenous Wnt2 inhibits CRC cell proliferation. Similarly, neutralizing secreted Wnt2 reduces Wnt target gene expression and suppresses CRC cell proliferation. Conversely, Wnt2 increases cell proliferation of intestinal epithelial cells. Intriguingly, WNT2 expression is transcriptionally silenced by EZH2-mediated H3K27me3 histone modification in non-CRC cells, However, WNT2 expression is de-repressed by the loss of PRC2's promoter occupancy in CRC cells. Our results reveal the unexpected roles of Wnt2 in complementing Wnt/β-catenin signaling for CRC cell proliferation.
Journal	Oncotarget
Volume Number	6
PubMed Central reference number	PMC4741928
Issue Number	35
PubMed reference number	26484565
e-ISSN	19492553
DOI	10.18632/oncotarget.6133
Language	English
Publisher	Impact Journals LLC
Publisher Date	2015-11-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: © 2015 Jung et al.
Subject Keyword	Wnt β-catenin Wnt2 colorectal cancer
Content Type	Text
Resource Type	Article
Subject	Oncology