Wnt2 complements Wnt/β-catenin signaling in colorectal cancer

Youn-Sang Jung; Sohee Jun; Sun Hye Lee; Amrish Sharma; Jae-Il Park

doi:10.18632/oncotarget.6133

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Research Papers:

Wnt2 complements Wnt/β-catenin signaling in colorectal cancer

Youn-Sang Jung, Sohee Jun, Sun Hye Lee, Amrish Sharma and Jae-Il Park _

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Oncotarget. 2015; 6:37257-37268. https://doi.org/10.18632/oncotarget.6133

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Abstract

Youn-Sang Jung1, Sohee Jun1, Sun Hye Lee1, Amrish Sharma1 and Jae-Il Park1,2,3

1 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2 Program in Genes and Development, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

3 Graduate School of Biomedical Sciences at Houston, The University of Texas Health Science Center and MD Anderson Cancer Center, Houston, TX, USA

Correspondence to:

Jae-Il Park, email:

Keywords: Wnt; β-catenin; Wnt2; colorectal cancer

Received: July 16, 2015 Accepted: September 23, 2015 Published: October 15, 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.

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Research Papers:

Wnt2 complements Wnt/β-catenin signaling in colorectal cancer

Abstract