Transcriptional Repressor DAXX Promotes Prostate Cancer Tumorigenicity via Suppression of Autophagy

Puto, Lorena A.; Brognard, John; Hunter, Tony

doi:10.1074/jbc.m115.658765

Cited by 35 publications

(37 citation statements)

References 56 publications

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“…However, in some cases, even researchers themselves argue that the precise identity of ALVA-31 is essential: “To exclude a cell type-specific effect, we extended ALVA-31 studies to other human PCa cell types” [38]. Subsequently, the authors explain how they used PC-3 cells in additional studies to ‘exclude cell type-specific effects’; in effect comparing two identical cell lines.…”

Section: Resultsmentioning

confidence: 99%

The ghosts of HeLa: How cell line misidentification contaminates the scientific literature

2017

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While problems with cell line misidentification have been known for decades, an unknown number of published papers remains in circulation reporting on the wrong cells without warning or correction. Here we attempt to make a conservative estimate of this ‘contaminated’ literature. We found 32,755 articles reporting on research with misidentified cells, in turn cited by an estimated half a million other papers. The contamination of the literature is not decreasing over time and is anything but restricted to countries in the periphery of global science. The decades-old and often contentious attempts to stop misidentification of cell lines have proven to be insufficient. The contamination of the literature calls for a fair and reasonable notification system, warning users and readers to interpret these papers with appropriate care.

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Section: Resultsmentioning

confidence: 99%

The ghosts of HeLa: How cell line misidentification contaminates the scientific literature

2017

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“…). Expression of Daxx has been studied in a variety of tumors . However, all the reported studies have been limited in that they were performed in vitro and in tumors other than gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, it has been reported that in neurons, the function of Daxx varies according to its localization: for example, when Daxx is located in the nucleus, it is antiapoptotic, whereas when it is localized in the cytoplasm, it is proapoptotic . Numerous studies have been conducted examining the expression of, or mutations in, Daxx in tumor tissues, such as in oral cancer, pancreatic neuroendocrine tumors, urothelial carcinoma, prostate cancer, and ovarian cancer amongst others . In tumor cells, Daxx is mainly located in the nucleus and is considered as a cancer‐promoting factor.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of Daxx NCR (Nuclear/Cytoplasmic Ratio) in gastric cancer

Zhao

et al. 2017

Cancer Medicine

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In addition to regulating apoptosis via its interaction with the death domain of Fas receptor, death domain associated protein 6 (Daxx) is also known to be involved in transcriptional regulation, suggesting that the function of Daxx depends on its subcellular localization. In this study, we aimed to explore Daxx subcellular localization in gastric cancer (GC) cells and correlate the findings with clinical data in GC patients. Seventy pairs of tissue samples (GC and adjacent normal tissue) were analyzed immunohistochemically for Daxx expression and localization (nuclear and cytoplasmic). The Daxx Nuclear/Cytoplasmic ratio (Daxx NCR) values in tissue microarray data with 522 tumor samples were further analyzed. The defined Prior cohort (n = 277, treatment between 2006 and 2009) and Recent cohort (n = 245, treatment between 2010 and 2011) were then used to examine the relationship between Daxx NCR and clinical data. The Daxx NCR was found to be clinically informative and significantly higher in GC tissue. Using Daxx NCR (risk ratio = 2.0), both the Prior and Recent cohorts were divided into high‐ and low‐risk groups. Relative to the low‐risk group, the high‐risk patients had a shorter disease free survival (DFS) and overall survival (OS) in both cohorts. Importantly, postoperative chemotherapy was found having differential effect on high‐ and low‐risk patients. Such chemotherapy brought no survival benefit, (and could potentially be detrimental,) to high‐risk patients after surgery. Daxx NCR could be used as a prognosis factor in GC patients, and may help select the appropriate population to benefit from chemotherapy after surgery.

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“…However, compared to many other studies including our own which generally show a combined incidence of ATRX/DAXX loss of no more than 43% [8,9,16,17], the 79% incidence of ATRX/DAXX-negative PanNETs appears unusually high. We postulate that [20,21]. In contrast, ATRX knockdown in in-vivo models of glioblastoma has been demonstrated to accelerate tumour growth and reduce survival in mice [22].…”

Section: Accepted Manuscriptmentioning

confidence: 93%

ATRX loss is an independent predictor of poor survival in pancreatic neuroendocrine tumors

et al. 2018

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Pancreatic neuroendocrine tumours (PanNETs) are rare neoplasms accounting for 1-2% of all pancreatic tumours. The biological behaviour of PanNETs is heterogeneous and unpredictable, adding to the difficulties of clinical management. The DAXX (death domain associated protein) and ATRX (alpha-thalassemia/mental retardation syndrome X-linked) genes encode proteins involved in SWI/SNF-like chromatin remodelling. Somatic inactivating mutations in DAXX and ATRX are frequent in PanNETs, mutually exclusive, and associated with telomere dysfunction resulting in genomic instability and alternate lengthening of telomeres. We sought to assess the clinical significance of the loss of the ATRX and DAXX proteins as determined by immunohistochemistry (IHC) in patients with PanNET. From an unselected cohort of 105 patients, we found ATRX loss in 10 tumours (9.5%) and DAXX loss in 16 (15.2%). DAXX and ATRX loss were confirmed mutually exclusive and associated with other adverse clinicopathological variables and poor survival in univariate analysis. In addition ATRX loss was also associated with higher AJCC stage and infiltrative tumour borders. However only ATRX loss, lymphovascular invasion and perineural spread were independent predictors of poor overall survival in multivariate analysis. In conclusion, loss of expression of ATRX as determined by IHC is a useful independent predictor of poor overall survival in PanNETs. Given its relative availability, ATRX loss as determined by IHC may have a role in routine clinical practice to refine prognostication in patients with PanNET.

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Transcriptional Repressor DAXX Promotes Prostate Cancer Tumorigenicity via Suppression of Autophagy

Cited by 35 publications

References 56 publications

The ghosts of HeLa: How cell line misidentification contaminates the scientific literature

The ghosts of HeLa: How cell line misidentification contaminates the scientific literature

Prognostic significance of Daxx NCR (Nuclear/Cytoplasmic Ratio) in gastric cancer

ATRX loss is an independent predictor of poor survival in pancreatic neuroendocrine tumors

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