Article: KRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomas

File Download Links for fulltext
(May Require Subscription)
Supplementary
  • Basic View
  • Metadata View
  • XML View
TitleKRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomas
AuthorsCheng, Y1
Geng, H1
Cheng, SH5
Liang, P5
Bai, Y4
Li, J1
Srivastava, G2
Ng, MHL5
Fukagawa, T3
Wu, X4
Chan, ATC1
Tao, Q1
Issue Date2010
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
CitationCancer Research, 2010, v. 70 n. 16, p. 6516-6526 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-09-4566
AbstractZinc finger transcription factors are involved broadly in development and tumorigenesis. Here, we report that the little studied zinc finger transcription factor ZNF382 functions as a tumor suppressor in multiple carcinomas. Although broadly expressed in normal tissues, ZNF382 expression was attenuated in multiple carcinoma cell lines due to promoter CpG methylation. ZNF382 was also frequently methylated in multiple primary tumors (nasopharyngeal, esophageal, colon, gastric, and breast). Ectopic expression of ZNF382 in silenced tumor cells significantly inhibited their clonogenicity and proliferation and induced apoptosis. We further found that ZNF382 inhibited NF-κB and AP-1 signaling and downregulated the expression of multiple oncogenes including MYC, MITF, HMGA2, and CDK6, as well as the NF-κB upstream factors STAT3, STAT5B, ID1, and IKBKE, most likely through heterochromatin silencing. ZNF382 could suppress tumorigenesis through heterochromatin-mediated silencing, as ZNF382 was colocalized and interacted with heterochromatin protein HP1 and further changed the chromatin modifications of ZNF382 target oncogenes. Our data show that ZNF382 is a functional tumor suppressor frequently methylated in multiple carcinomas. ©2010 AACR.
ISSN0008-5472
2011 Impact Factor: 7.856
2011 SCImago Journal Rankings: 1.309
DOIhttp://dx.doi.org/10.1158/0008-5472.CAN-09-4566
ISI Accession Number IDWOS:000280887000014
Funding AgencyGrant Number
Chinese University of Hong Kong474407
Funding Information:

Hong Kong RGC grant 474407, Chinese University of Hong Kong Scheme C, and a Chinese University of Hong Kong direct grant.

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorCheng, Y
dc.contributor.authorGeng, H
dc.contributor.authorCheng, SH
dc.contributor.authorLiang, P
dc.contributor.authorBai, Y
dc.contributor.authorLi, J
dc.contributor.authorSrivastava, G
dc.contributor.authorNg, MHL
dc.contributor.authorFukagawa, T
dc.contributor.authorWu, X
dc.contributor.authorChan, ATC
dc.contributor.authorTao, Q
dc.date.accessioned2010-12-23T08:38:28Z
dc.date.available2010-12-23T08:38:28Z
dc.date.issued2010
dc.description.abstractZinc finger transcription factors are involved broadly in development and tumorigenesis. Here, we report that the little studied zinc finger transcription factor ZNF382 functions as a tumor suppressor in multiple carcinomas. Although broadly expressed in normal tissues, ZNF382 expression was attenuated in multiple carcinoma cell lines due to promoter CpG methylation. ZNF382 was also frequently methylated in multiple primary tumors (nasopharyngeal, esophageal, colon, gastric, and breast). Ectopic expression of ZNF382 in silenced tumor cells significantly inhibited their clonogenicity and proliferation and induced apoptosis. We further found that ZNF382 inhibited NF-κB and AP-1 signaling and downregulated the expression of multiple oncogenes including MYC, MITF, HMGA2, and CDK6, as well as the NF-κB upstream factors STAT3, STAT5B, ID1, and IKBKE, most likely through heterochromatin silencing. ZNF382 could suppress tumorigenesis through heterochromatin-mediated silencing, as ZNF382 was colocalized and interacted with heterochromatin protein HP1 and further changed the chromatin modifications of ZNF382 target oncogenes. Our data show that ZNF382 is a functional tumor suppressor frequently methylated in multiple carcinomas. ©2010 AACR.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationCancer Research, 2010, v. 70 n. 16, p. 6516-6526 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-09-4566
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.CAN-09-4566
dc.identifier.epage6526
dc.identifier.hkuros176922
dc.identifier.isiWOS:000280887000014
Funding AgencyGrant Number
Chinese University of Hong Kong474407
Funding Information:

Hong Kong RGC grant 474407, Chinese University of Hong Kong Scheme C, and a Chinese University of Hong Kong direct grant.

dc.identifier.issn0008-5472
2011 Impact Factor: 7.856
2011 SCImago Journal Rankings: 1.309
dc.identifier.issue16
dc.identifier.openurl
dc.identifier.pmid20682794
dc.identifier.scopuseid_2-s2.0-77955728660
dc.identifier.spage6516
dc.identifier.urihttp://hdl.handle.net/10722/129528
dc.identifier.volume70
dc.languageeng
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
dc.publisher.placeUnited States
dc.relation.ispartofCancer Research
dc.relation.referencesReferences in Scopus
dc.subject.meshAnimals
dc.subject.meshDNA-Binding Proteins - biosynthesis - genetics
dc.subject.meshGenes, Tumor Suppressor
dc.subject.meshNeoplasms, Multiple Primary - genetics - metabolism - pathology
dc.subject.meshTranscription Factors - biosynthesis - genetics
dc.titleKRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomas
dc.typeArticle
Author Affiliations
  1. Li Ka Shing Institute of Health Sciences
  2. The University of Hong Kong
  3. Sokendai Graduate University for Advanced Studies
  4. Hunan Normal University
  5. Chinese University of Hong Kong