Abstract
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.
Keywords:
Esophageal carcinogenesis; Esophageal squamous cell carcinoma; HOXA13; Oncogenic hallmarks.
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinogenesis / genetics*
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Carcinogenesis / metabolism
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Carcinogenesis / pathology
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Carcinoma, Squamous Cell / genetics*
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / mortality
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Carcinoma, Squamous Cell / pathology
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Cell Adhesion
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Cell Differentiation
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Cell Line, Transformed
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Cell Movement
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Esophageal Neoplasms / genetics*
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Esophageal Neoplasms / metabolism
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Esophageal Neoplasms / mortality
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Esophageal Neoplasms / pathology
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Esophagus / metabolism
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Esophagus / pathology
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic*
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / metabolism
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism
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Humans
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Keratin-19 / genetics
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Keratin-19 / metabolism
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Keratinocytes / metabolism
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Keratinocytes / pathology
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Neoplasm Proteins / classification
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Protein Precursors / genetics
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Protein Precursors / metabolism
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Signal Transduction
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Spheroids, Cellular / metabolism
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Spheroids, Cellular / pathology
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Survival Analysis
Substances
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Histocompatibility Antigens Class I
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Homeodomain Proteins
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KRT19 protein, human
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Keratin-19
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Neoplasm Proteins
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Phosphoproteins
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Protein Precursors
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homeobox protein HOXA13
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involucrin