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Forced expression of HOXA13 confers oncogenic hallmarks to esophageal keratinocytes.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 4.2 ) Pub Date : 2020-03-25 , DOI: 10.1016/j.bbadis.2020.165776
Kateryna Nesteruk 1 , Vincent T Janmaat 1 , Hui Liu 1 , Timo L M Ten Hagen 1 , Maikel P Peppelenbosch 1 , Gwenny M Fuhler 2
Affiliation  

HOXA13 overexpression has been detected in human ESCC tissue and high HOXA13 protein expression is correlated with a shorter median survival time in ESCC patients. Although aberrant expression of HOXA13 in ESCC has thus been established, little is known regarding the functional consequences thereof. The present study aimed to examine to what extent aberrant HOXA13 might drive carcinogenesis in esophageal keratinocytes. To this end, we overexpressed HOXA13 in a non-transformed human esophageal cell line EPC2-hTERT, performed gene expression profiling to identify key processes and functions, and performed functional experiments. We found that HOXA13 expression confers oncogenic hallmarks to esophageal keratinocytes. It provides proliferation advantage to keratinocytes, reduces sensitivity to chemical agents, regulates MHC class I expression and differentiation status and promotes cellular migration. Our data indicate a crucial role of HOXA13 at early stages of esophageal carcinogenesis.

中文翻译:

HOXA13的强制表达赋予食管角化细胞致癌标志。

在人类ESCC组织中已经检测到HOXA13过表达,并且高HOXA13蛋白表达与ESCC患者中较短的中位生存时间相关。虽然已经建立了HOXA13在ESCC中的异常表达,但对其功能后果知之甚少。本研究旨在检查HOXA13异常可能在多大程度上驱动食管角质形成细胞的癌变。为此,我们在未转化的人食道细胞系EPC2-hTERT中过表达HOXA13,进行基因表达谱分析以鉴定关键过程和功能,并进行功能实验。我们发现HOXA13表达赋予食管角质形成细胞致癌标志。它为角质形成细胞提供增殖优势,降低了对化学试剂的敏感性,调节MHC I类表达和分化状态并促进细胞迁移。我们的数据表明HOXA13在食管癌变的早期阶段起着至关重要的作用。
更新日期:2020-03-25
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