RGD Reference Report - Death domain-associated protein DAXX promotes ovarian cancer development and chemoresistance. - Rat Genome Database

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Death domain-associated protein DAXX promotes ovarian cancer development and chemoresistance.

Authors: Pan, WW  Zhou, JJ  Liu, XM  Xu, Y  Guo, LJ  Yu, C  Shi, QH  Fan, HY 
Citation: Pan WW, etal., J Biol Chem. 2013 May 10;288(19):13620-30. doi: 10.1074/jbc.M112.446369. Epub 2013 Mar 28.
RGD ID: 9587820
Pubmed: PMID:23539629   (View Abstract at PubMed)
PMCID: PMC3650397   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M112.446369   (Journal Full-text)

BACKGROUND: The role of DAXX in ovarian cancer development and metastasis has not been investigated before now. RESULTS: Overexpression of DAXX enhanced ovarian cancer cell proliferation, colony formation, and migration, whereas Daxx depletion had the opposite effects. CONCLUSION: DAXX promotes ovarian cancer cell proliferation and chemoresistance. SIGNIFICANCE: ModulatingDAXXmay be an effective strategy for preventing the recurrence and chemoresistance of ovarian cancers. Understanding the genes involved in apoptosis and DNA damage responses may improve therapeutic strategies for ovarian cancer. The death domain-associated protein DAXX can be either a pro-apoptotic or an anti-apoptotic factor, depending on the cell type and context. In this study, we found that DAXX was highly expressed in human ovarian surface epithelial tumors but not in granulosa cell tumors. In cultured ovarian cancer cells, DAXX interacted with promyelocytic leukemia protein (PML) and localized to subnuclear domains (so-called PML nuclear bodies). A role for DAXX in ovarian cancer cell proliferation, metastasis, and radio/chemoresistance was examined. Overexpression of DAXX enhanced multiple ovarian cancer cell lines' proliferation, colony formation, and migration, whereas Daxx depletion by RNA interference had the opposite effects. When transplanted into nude mice, ovarian cancer cells that overexpressed DAXX displayed enhanced tumorigenesis capability in vivo, whereas Daxx depletion inhibited tumor development. Importantly, Daxx induced tumorigenic transformation of normal ovarian surface epithelial cells. Daxx also protected ovarian cancer cells against x-irradiation- and chemotherapy-induced DNA damage by interacting with PML. Taken together, our results suggest that DAXX is a novel ovarian cancer oncogene that promotes ovarian cancer cell proliferation and chemoresistance in ovarian cancer cells. Thus, modulating DAXX-PML nuclear body activity may be an effective strategy for preventing the recurrence and chemoresistance of ovarian cancers.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DAXXHumanclear cell adenocarcinoma  IEP protein:increased expression:ovary:RGD 
DaxxRatclear cell adenocarcinoma  ISODAXX (Homo sapiens)protein:increased expression:ovary:RGD 
DaxxMouseclear cell adenocarcinoma  ISODAXX (Homo sapiens)protein:increased expression:ovary:RGD 
DAXXHumanEndometrioid Carcinomas  IEP protein:increased expression:ovary:RGD 
DaxxRatEndometrioid Carcinomas  ISODAXX (Homo sapiens)protein:increased expression:ovary:RGD 
DaxxMouseEndometrioid Carcinomas  ISODAXX (Homo sapiens)protein:increased expression:ovary:RGD 
DAXXHumanMucinous Cystadenoma  IEP protein:increased expression:ovary:RGD 
DaxxRatMucinous Cystadenoma  ISODAXX (Homo sapiens)protein:increased expression:ovary:RGD 
DaxxMouseMucinous Cystadenoma  ISODAXX (Homo sapiens)protein:increased expression:ovary:RGD 
DAXXHumanNeoplasm Metastasis  IMP  RGD 
DaxxRatNeoplasm Metastasis  ISODAXX (Homo sapiens) RGD 
DaxxMouseNeoplasm Metastasis  ISODAXX (Homo sapiens) RGD 
DAXXHumanovary epithelial cancer  IDA  RGD 
DaxxRatovary epithelial cancer  ISODAXX (Homo sapiens) RGD 
DaxxMouseovary epithelial cancer  ISODAXX (Homo sapiens) RGD 
DAXXHumanSerous Cystadenoma  IEP protein:increased expression:ovary:RGD 
DaxxRatSerous Cystadenoma  ISODAXX (Homo sapiens)protein:increased expression:ovary:RGD 
DaxxMouseSerous Cystadenoma  ISODAXX (Homo sapiens)protein:increased expression:ovary:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Daxx  (death-domain associated protein)

Genes (Mus musculus)
Daxx  (Fas death domain-associated protein)

Genes (Homo sapiens)
DAXX  (death domain associated protein)


Additional Information