Daxx regulates mitotic progression and prostate cancer predisposition

Kwan, Pak Shing; Lau, Chi Chiu; Chiu, Yung Tuen; Man, Cornelia; Liu, Ji; Tang, Kai Dun; Wong, Yong Chuan; Ling, Ming-Tat

doi:10.1093/carcin/bgs391

Cited by 34 publications

(33 citation statements)

References 29 publications

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“…Furthermore, its ectopic expression in a non-malignant prostate epithelial cell line induced polyploidy under mitotic stress. Daxx may promote chromosome instability during prostate cancer development [12]. So it implies Daxx might play a critical role in the cellular transformation and cancer development.…”

Section: Discussionmentioning

confidence: 99%

Distribution and location of Daxx in cervical epithelial cells with high risk human papillomavirus positive

Tang

et al. 2014

Diagn Pathol

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AimsTo provide the basis for further exploring the effect and its mechanism of Death domain associated protein (Daxx) on the progress of cervical carcinoma induced by human papillomavirus (HPV), the distribution and location of Daxx in cervical carcinoma with high risk HPV(HR-HPV) positive was analyzed.MethodsThe samples of normal cervical epithelial cells, cervical intraepithelial neoplasia grade I (CINI), CINII CINIII and cervical cancers were collected. Immunohistochemistry assay was used to analyze the distributions and locations of Daxx in the cervical tissue. Indirect immunoinfluorescence test was utilized to observe the locations of Daxx in Caski cells with HPV16 positive.ResultsUnder the light microscopy, the brown signals of Daxx distributed in the nuclei of normal cervical epithelial cells; Daxx mainly distributed in nuclear membrane and there were a small amount of Daxx in the nuclei in CINI. Daxx intensively distributed in the cytoplasm and cell membrane in CINII, CINIII and cervical cancer. Under fluorescent microscopy, the distribution and location of Daxx in Caski cells was similarly to that in cervical cells of CINII, CINIII and cervical cancer.ConclusionIn the progress of the cervical cancer, Daxx gradually translocates from nucleus into nuclear membrane, cytoplasm and cell membrane. Daxx locates in the cytoplasm and cell membrane in CINII, CINIII and cervical cancer.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/4671548951113870.

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Section: Discussionmentioning

confidence: 99%

Distribution and location of Daxx in cervical epithelial cells with high risk human papillomavirus positive

Tang

et al. 2014

Diagn Pathol

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“…One study has shown that Daxx, an APC inhibitor, interacts with Cdc20 and inhibits the degradation of APC Cdc20 substrates, leading to a transient delay in mitotic progression and chromosome instability (Kwan et al, 2013). Consistently, Daxx is overexpressed in prostate cancer tissues and positively correlated with the Gleason score and metastasis (Kwan et al, 2013). Moreover, LATs (L-type amino acid transporters) protein was expressed at all stages of prostate cancer.…”

Section: Role Of Cdc20 In Human Malignanciesmentioning

confidence: 99%

Targeting Cdc20 as a novel cancer therapeutic strategy

Wang

Zhang

Wan

et al. 2015

Pharmacology & Therapeutics

199

176

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The Anaphase Promoting Complex (APC, also called APC/C) regulates cell cycle progression by forming two closely related, but functionally distinct E3 ubiquitin ligase sub-complexes, APCCdc20 and APCCdh1, respectively. Emerging evidence has begun to reveal that Cdc20 and Cdh1 have opposing functions in tumorigenesis. Specifically, Cdh1 functions largely as a tumor suppressor, whereas Cdc20 exhibits an oncogenic function, suggesting that Cdc20 could be a promising therapeutic target for combating human cancer. However, the exact underlying molecular mechanisms accounting for their differences in tumorigenesis remain largely unknown. Therefore, in this review, we summarize the downstream substrates of Cdc20 and the critical functions of Cdc20 in cell cycle progression, apoptosis, ciliary disassembly and brain development. Moreover, we briefly describe the upstream regulators of Cdc20 and the oncogenic role of Cdc20 in a variety of human malignancies. Furthermore, we summarize multiple pharmacological Cdc20 inhibitors including TAME and Apcin, and their potential clinical benefits. Taken together, development of specific Cdc20 inhibitors could be a novel strategy for the treatment of human cancers with elevated Cdc20 expression.

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“…In prostate tissues, DAXX staining intensity is stronger in areas surrounding tumor glands compared to areas surrounding normal glands [16]. Moreover, strong positive DAXX staining has been observed in PCa tissues, compared to benign prostatic hyperplasia (BPH) tissues, suggesting that DAXX is overexpressed in PCa [17]. In prostate cells, DAXX levels are increased in various PCa cell lines, relative to nontumorigenic human prostatic epithelial lines [17; Submitted].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, strong positive DAXX staining has been observed in PCa tissues, compared to benign prostatic hyperplasia (BPH) tissues, suggesting that DAXX is overexpressed in PCa [17]. In prostate cells, DAXX levels are increased in various PCa cell lines, relative to nontumorigenic human prostatic epithelial lines [17; Submitted]. Conversely, in cells and tissues, DAPK1 and DAPK3 are downregulated in cancer contexts [18; Submitted].…”

Section: Introductionmentioning

confidence: 99%

The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer

2015

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While carcinoma of the prostate is the second most common cause of cancer death in the US, current methods and markers used to predict prostate cancer (PCa) outcome are inadequate. This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. In conclusion, DAXX binds active regulatory elements and co-localizes with DNMT1 in the prostate cancer genome. Given DAXX's putative regulatory role in autophagy, future studies may consider DAXX as a candidate marker and therapeutic target for prostate cancer.

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Daxx regulates mitotic progression and prostate cancer predisposition

Cited by 34 publications

References 29 publications

Distribution and location of Daxx in cervical epithelial cells with high risk human papillomavirus positive

Distribution and location of Daxx in cervical epithelial cells with high risk human papillomavirus positive

Targeting Cdc20 as a novel cancer therapeutic strategy

The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer

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