ZNF217 suppresses cell death associated with chemotherapy and telomere dysfunction

Huang, Guanhao; Krig, Sheryl R.; Kowbel, David; Xu, Hongmei; Hyun, Bill; Volik, Stas; Feuerstein, Burt G.; Mills, Gordon B.; Stokoe, David; Yaswen, Paul

doi:10.1093/hmg/ddi352

Cited by 58 publications

(72 citation statements)

References 20 publications

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“…ZNF217 overexpression may indirectly affect gene regulation by disrupting the function of other transcription factors that, under normal conditions, require co-repressors such as CoREST. While this paper was in preparation, ZNF217 overexpression was demonstrated to function in the suppression of apoptosis associated with chemotherapeutic treatment and increased phosphorylation of Akt, further demonstrating its importance in cancer progression (Huang et al, 2005).…”

Section: Discussionmentioning

confidence: 90%

Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: identification of a ZNF217 consensus recognition sequence

et al. 2006

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Zinc-finger protein 217 (ZNF217) is a Kruppel-like zincfinger protein located at 20q13.2, within a region of recurrent maximal amplification. Here, we demonstrate that ZNF217 is a transcriptional repressor protein and report the purification and characterization of a ZNF217 complex. The purified ZNF217 complex consists of approximately six proteins and contains the transcriptional co-repressors CoREST, BHC110/LSD1, histone deacetylase (HDAC) 2 and C-terminal binding protein (CtBP1). The purified ZNF217 complex possesses deacetylase activity as well as lysine 4 histone H3-specific demethylase activity that is most likely mediated by the BHC110/LSD1 component. To determine if ZNF217 is a sequence-specific binding protein, we have made use of cyclic amplification and selection of targets (CAST) assay and identify for the first time a ZNF217 DNA consensus recognition sequence (CRS) that is highly conserved in the human E-cadherin promoter. Chromatin immunoprecipitation (ChIP) experiments demonstrate that ZNF217, as well as the other components of the ZNF217 complex, are found on the region of the proximal E-cadherin promoter that contains the identified ZNF217 CRS in vivo. Using a combination of transient transfections and small interfering RNA, we demonstrate that ZNF217 represses the E-cadherin promoter. Collectively, our results implicate ZNF217 and its associated proteins in a novel pathway that may have profound effects on cancer progression.

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Section: Discussionmentioning

confidence: 90%

Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: identification of a ZNF217 consensus recognition sequence

et al. 2006

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“…14 ZNF217 overexpression can cause cellular immortalization, telomerase repression, antiapoptosis and increased metastatic potential. 29,30 Recently, Krig et al 31 reported that ZNF217 could activate the PI3K-Akt pathway by regulating ErbB3 expression in breast cancer cells. ZNF217 amplification and PIK3CA mutations were almost mutually exclusive in the study by Rahman et al 32 In our study, the correlation between PIK3CA mutations and ZNF217 amplification was not statistically significant (data not shown, P ¼ 0.541).…”

Section: Discussionmentioning

confidence: 99%

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

et al. 2014

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AT-rich interactive domain 1A (ARID1A) is a subunit of switch/sucrose non-fermentable (SWI/SNF) complex. Recently, alterations of ARID1A gene, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway and zinc-finger protein 217 (ZNF217) gene have been identified as frequent molecular genetic changes in ovarian clear cell carcinoma. The relationships between these events have not been studied and integrated in the same cohort. This study was aimed at determining the correlation between these molecular events and other clinicopathological factors, including the prognostic impacts of these clinicopathological factors. A total of 68 ovarian clear cell carcinoma cases were collected and subjected to immunohistochemistry testing for ARID1A, SMARCA2, SMARCA4, SMARCB1 and phosphatase and tensin homolog (PTEN), mutation analysis for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene and fluorescence in situ hybridization for ZNF217 amplification. The correlations between ARID1A expression, PI3K-Akt pathway, ZNF217 amplification and other clinicopathological factors were analyzed. Loss of ARID1A expression was present in 35 cases (52%) and loss of SMARCA2 expression occurred in 1 case. SMARCA4 and SMARCB1 expressions were preserved in all cases. PIK3CA mutations were present in 23 cases (34%) and loss of PTEN expression occurred in 8 cases (12%). Alterations in the PI3K-Akt pathway (PIK3CA mutations or loss of PTEN expression) were found in 42 cases (62%). ZNF217 amplification was detected in 21 cases (31%). Loss of ARID1A expression was significantly related to younger patient age (P ¼ 0.048), PI3K-Akt pathway activation (P ¼ 0.046) and ZNF217 amplification (P ¼ 0.028). All of the clinicopathological factors were not prognostic factors for ovarian clear cell carcinoma after multivariate analysis, except International Federation of Gynecology and Obstetrics staging (P ¼ 0.001). Our results showed that loss of ARID1A expression usually coexisted with PI3K-Akt pathway activation and/or ZNF217 amplification. Synergic effects of loss of ARID1A and PI3K-Akt pathway activation as well as ZNF217 amplification may be related to the development of ovarian clear cell carcinoma.

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“…In clear cell ovarian carcinoma ZNF217 overexpression was strongly related to poor prognosis upon platinum agent-based chemotherapy [61]. ZNF217 suppresses chemotherapy-induced cell death, promoting doxorubicin and paclitaxel resistance in breast cancer [87, 88]. Triciribine, a nucleoside analog and AKT inhibitor effectively kills chemoresistant cancer cells overexpressing ZNF217 [87].…”

Section: Potential Targetable Pathwaysmentioning

confidence: 99%

Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

2016

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Olfactory neuroblastoma (ONB, Esthesioneuroblastoma) is an infrequent neoplasm of the head and neck area derived from olfactory neuroepithelium. Despite relatively good prognosis a subset of patients shows recurrence, progression and/or metastatic disease, which requires additional treatment. However, neither prognostic nor predictive factors are well specified. Thus, we performed a literature search for the currently available data on disturbances in molecular pathways, cytogenetic changes and results gained by next generation sequencing (NGS) approaches in ONB in order to gain an overview of genetic alterations which might be useful for treating patients with ONB. We present briefly ONB molecular pathogenesis and propose potential therapeutic targets and prognostic factors. Possible therapeutic targets in ONB include: receptor tyrosine kinases (c-kit, PDGFR-b, TrkB; EGFR); somatostatin receptor; FGF-FGFR1 signaling; Sonic hedgehog pathway; apoptosis-related pathways (Bcl-2, TRAIL) and neoangiogenesis (VEGF; KDR). Furthermore, we compare high- and low-grade ONB, and describe its frequent mimicker: sinonasal neuroendocrine carcinoma. ONB is often a therapeutic challenge, so our goal should be the implementation of acquired knowledge into clinical practice, especially at pretreated, recurrent and metastatic stages. Moreover, the multicenter molecular studies are needed to increase the amount of available data.

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ZNF217 suppresses cell death associated with chemotherapy and telomere dysfunction

Cited by 58 publications

References 20 publications

Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: identification of a ZNF217 consensus recognition sequence

Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: identification of a ZNF217 consensus recognition sequence

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

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