Loss of GATA6 leads to nuclear deformation and aneuploidy in ovarian cancer.
A prominent hallmark of most human cancer is aneuploidy, which is a result of the chromosomal instability of cancer cells and is thought to contribute to the initiation and progression of most carcinomas. The developmentally regulated GATA6 transcription factor is commonly lost in ovarian cancer, and the loss of its expression is closely associated with neoplastic transformation of the ovarian surface epithelium. In the present study, we found that reduction of GATA6 expression with small interfering RNA (siRNA) in human ovarian surface epithelial cells resulted in deformation of the nuclear envelope, failure of cytokinesis, and formation of polyploid and aneuploid cells. We further discovered that loss of the nuclear envelope protein emerin may mediate the consequences of GATA6 suppression. The nuclear phenotypes were reproduced by direct suppression of emerin with siRNA. Thus, we conclude that diminished expression of GATA6 leads to a compromised nuclear envelope that is causal for polyploidy and aneuploidy in ovarian tumorigenesis. The loss of emerin may be the basis of nuclear morphological deformation and subsequently the cause of aneuploidy in ovarian cancer cells.
Capo-chichi
Callinice D
CD
Sylvester Comprehensive Cancer Center, Department of Medicine, and Department of Obstetrics and Gynecology, University of Miami School of Medicine, Miami, Florida 33136, USA.
Cai
Kathy Q
KQ
Testa
Joseph R
JR
Godwin
Andrew K
AK
Xu
Xiang-Xi
XX
D000782:Aneuploidy; D002467:Cell Nucleus / Q000473:pathology* / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D043171:Chromosomal Instability; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology; D005260:Female; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D010053:Ovary / Q000166:cytology; D010641:Phenotype; D011123:Polyploidy; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D050993:GATA6 Transcription Factor; D006657:Histones; D008565:Membrane Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C092710:emerin