Wnt2 complements Wnt/β-catenin signaling in colorectal cancer.
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.
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Youn-Sang
YS
Jung
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sohee
S
Jun
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sun Hye
SH
Lee
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Amrish
A
Sharma
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Program in Genes and Development, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Graduate School of Biomedical Sciences at Houston, The University of Texas Health Science Center and MD Anderson Cancer Center, Houston, TX, USA.
Jae-Il
JI
Park
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019898:Autocrine Communication; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008745:Methylation; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D060449:Wnt Signaling Pathway; D051154:Wnt2 Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495270:CTNNB1 protein, human; D006657:Histones; C495244:WNT2 protein, human; D051154:Wnt2 Protein; D051176:beta Catenin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
Wnt; Wnt2; colorectal cancer; β-catenin