Show simple item record

dc.contributor.authorXie, Guofeng
dc.contributor.authorPeng, Zhongsheng
dc.contributor.authorLiang, Jinqing
dc.contributor.authorLarabee, Shannon M
dc.contributor.authorDrachenberg, Cinthia B
dc.contributor.authorYfantis, Harris
dc.contributor.authorRaufman, Jean-Pierre
dc.date.accessioned2022-03-02T14:20:47Z
dc.date.available2022-03-02T14:20:47Z
dc.date.issued2022-02-22
dc.identifier.urihttp://hdl.handle.net/10713/18134
dc.description.abstractSustained proliferative signaling and resisting cell death are hallmarks of cancer. Zinc finger protein 277 (ZNF277; murine Zfp277), a transcription factor regulating cellular senescence, is overexpressed in colon cancer, but its actions in intestinal homeostasis and neoplasia are unclear. Using human and murine intestine, human colon cancer cells, and Apc Min/+ mice with dysregulated β-catenin signaling and exuberant intestinal neoplasia, we explored the actions of ZNF277/Zfp277 and defined the underlying mechanisms. In normal human and murine intestine, ZNF277/Zfp277 was expressed uniquely in early stem cell progenitors, undifferentiated transit-amplifying cells (TACs). Zfp277 was overexpressed in the Apc Min/+ mouse colon, implicating ZNF277/Zfp277 as a transcriptional target of β-catenin signaling. We confirmed this by showing β-catenin knockdown reduced ZNF277 expression and, using chromatin IP, identified 2 β-catenin binding sites in the ZNF277 promoter. Zfp277 deficiency attenuated intestinal epithelial cell proliferation and tumor formation, and it strikingly prolonged Apc Min/+ mouse survival. RNA-Seq and PCR analyses revealed that Zfp277 modulates expression of genes in key cancer pathways, including β-catenin signaling, the HOXD family that regulates development, and p21WAF1, a cell cycle inhibitor and tumor suppressor. In both human colon cancer cells and the murine colon, ZNF277/Zfp277 deficiency induced p21WAF1 expression and promoted senescence. Our findings identify ZNF277/Zfp277 as both a TAC marker and colon cancer oncogene that regulates cellular proliferation and senescence, in part by repressing p21WAF1 expression. © 2022, Xie et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.en_US
dc.description.urihttps://doi.org/10.1172/jci.insight.150894en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.ispartofJCI Insighten_US
dc.subjectCellular senescenceen_US
dc.subjectColorectal canceren_US
dc.subjectGastroenterologyen_US
dc.subjectOncologyen_US
dc.titleZinc finger protein 277 is an intestinal transit-amplifying cell marker and colon cancer oncogene.en_US
dc.typeArticleen_US
dc.identifier.doi10.1172/jci.insight.150894
dc.identifier.pmid35015732
dc.source.journaltitleJCI insight
dc.source.volume7
dc.source.issue4
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States


This item appears in the following Collection(s)

Show simple item record