ZNF750 is a lineage-specific tumour suppressor in squamous cell carcinoma

Hazawa, Masaharu; Dong, Lin; Handral, Harish K; Xu, Lu; Chen, Y; Yy, Jiang; Mayakonda, Anand; Ding, Ling-Wen; Meng, Xuan; Sharma, Arjun; Samuel, Shaija; Mm, Movahednia; Wong, Richard W.; Yang, Henry; Tong, Chao; Koeffler, H. Phillip

doi:10.1038/onc.2016.377

Cited by 98 publications

(101 citation statements)

References 21 publications

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“…Several reports have shown that the expression of ZNF750 is decreased in cancer tissues compared with normal tissues [5,6,10], and the mutation of ZNF750 inhibited the activation of differentiation genes and caused functional deterioration [9,14]. Some studies have shown that the decreased expression of ZNF750 promoted cell growth, migration, and invasion in squamous cell carcinoma [5,6,10], and Cohen et al [15] revealed that the downregulation of ZNF750 decreased apoptosis in human keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of ZNF750 was immunohistochemically assessed using the peroxidase-antiperoxidase complex method in accordance with the previously reported protocol [10]. Antihuman ZNF750 polyclonal antibody (1: 200; HPA023012; SigmaAldrich, St. Louis, MO, USA) was used as the primary antibody, and anti-mouse/rabbit antibody (EnVision/HRP, anti-mouse/rabbit, K5001; DAKO Japan, Tokyo, Japan) was used as the secondary antibody.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…ZNF750 was reported to act as a transcriptional regulator of epidermal differentiation, and the expression of ZNF750 induces epidermal differentiation genes and suppresses epidermal progenitor genes [9]. ZNF750 has been shown to function as a tumor suppressor [5,6,10], and we previously reported the relationship between ZNF750 expression and chemoradiotherapy response in ESCC patients [11]. We, therefore, consider ZNF750 to be a notable gene in the field of ESCC.…”

Section: Introductionmentioning

confidence: 99%

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ZNF750 Expression Is a Potential Prognostic Biomarker in Esophageal Squamous Cell Carcinoma

Otsuka

Akutsu²,

Sakata³

et al. 2017

Oncology

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Objective: ZNF750, a transcriptional regulator of epidermal differentiation, has been identified as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the clinical and prognostic significance of ZNF750 expression and to evaluate the effect of ZNF750 knockdown on cell proliferation, migration, and invasion in ESCC. Methods: A total of 124 patients with ESCC who underwent curative esophagectomy were evaluated in this study. The expression of ZNF750 in surgical specimens was immunohistochemically assessed and used in the analysis of clinicopathological features and overall survival (OS). The molecular role of ZNF750 was investigated by ZNF750 knockdown using small interfering RNA (siRNA) in ESCC cell lines. Results: Low ZNF750 expression had a significant correlation with positive lymph node metastasis (p = 0.028). Furthermore, there was a significant relationship between low expression of ZNF750 in ESCC and a poor OS, and a multivariate analysis showed that low ZNF750 expression was an independent prognostic factor (p = 0.020). The cell growth, migration, and invasion were significantly increased by downregulation of ZNF750. Conclusions: The low expression of ZNF750 was significantly associated with a poor prognosis, and ZNF750 expression may, therefore, be a reliable prognostic biomarker in ESCC.

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Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

ZNF750 Expression Is a Potential Prognostic Biomarker in Esophageal Squamous Cell Carcinoma

Otsuka

Akutsu²,

Sakata³

et al. 2017

Oncology

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“…As several reports have shown, ZNF750 interacts with KLF4 to induce differentiation genes [14,25,26] . KLF4 is a member of the Krüppel-type zinc finger transcription factor family [27][28][29] .…”

Section: Discussionmentioning

confidence: 99%

ZNF750 Expression as a Novel Candidate Biomarker of Chemoradiosensitivity in Esophageal Squamous Cell Carcinoma

et al. 2017

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Objective: ZNF750, an epidermal differentiation regulator, has been suggested to act as a tumor suppressor of esophageal squamous cell carcinoma (ESCC). Although a correlation between the epidermal differentiation gene and resistance to chemoradiotherapy (CRT) has been posited, no data regarding the ZNF750 status in ESCC have been reported. The aim of the present study was to evaluate the relationship between ZNF750 expression and response to CRT in ESCC. Methods: Eighty-seven patients who had been pathologically diagnosed with ESCC were evaluated in the present study. All patients underwent neoadjuvant CRT, followed by curative esophagectomy. The expression of ZNF750 in pretreatment biopsy samples was immunohistochemically investigated and compared to the histopathological effectiveness of CRT in surgical specimens. Results: High expression of ZNF750 was closely correlated with good sensitivity to CRT (p = 0.016). A univariate analysis showed that high/intermediate expression of ZNF750 was a significant predictive factor for good sensitivity to CRT (p = 0.006). High/intermediate expression of ZNF750 (30% or more) remained an independent predictive factor for sensitivity to CRT in a multivariate analysis (p = 0.033). Conclusions: ZNF750 expression predicts sensitivity to CRT and can be a biomarker that reliably predicts the response of ESCC to CRT.

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“…In addition, in silico analysis showed that ESCC individuals with ZNF750 mutations were more likely to present LN metastasis, and to have shorter disease-free survival compared with those without ZNF750 mutations. ZNF750 is a novel tumor suppressor identified by our lab and others (5,11,12), and it exhibits frequent loss-of-function mutations and genomic deletions across different types of squamous cell carcinomas in a lineage-specific fashion. In vitro experiments have shown that ZNF750 regulates the proliferation, differentiation, adhesion and migration of squamous cells, supporting its putative role in tumor metastasis.…”

mentioning

confidence: 99%