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.

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Keywords Esophageal carcinogenesis, Esophageal squamous cell carcinoma, HOXA13, Oncogenic hallmarks
Persistent URL dx.doi.org/10.1016/j.bbadis.2020.165776, hdl.handle.net/1765/126888
Journal Biochimica et Biophysica Acta - Molecular Basis of Disease
Nesteruk, K. (Kateryna), Janmaat, V.T, Liu, H, ten Hagen, T.L.M, Peppelenbosch, M.P, & Fuhler, G.M. (2020). Forced expression of HOXA13 confers oncogenic hallmarks to esophageal keratinocytes. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1866(8). doi:10.1016/j.bbadis.2020.165776