Increased aldehyde reductase expression mediates acquired radioresistance of laryngeal cancer cells via modulating p53

Cancer Biology & Therapy
Jae-Sung KimSang-Gu Hwang

Abstract

The main obstacle to cure tumors by radiotherapy has been ascribed to tumor radioresistance. To determine the mechanisms underlying resistance to irradiation, it is essential to compare proteins differentially expressed from radiotherapy-sensitive and -resistant cancer cells. Aldehyde reductase (AKR1A1) was recently identified as increased in radioresistant laryngeal cancer cells by comparative proteomics approach. Here, we provide the mechanism of AKR1A1-mediated radioresistance via p53 regulation in laryngeal cancer cells. AKR1A1 induction was correlated with the radioresistant phenotype of laryngeal cancer HEp-2 cells. AKR1A1 depletion with siRNA significantly enhanced radiation sensitivity of radioresistant HEp-2 cells by promoting radiation-induced cell death and accelerated radiation-mediated inhibition of cell proliferation, without affecting either the PI3K-Akt or MAPK-ERK pathways. Intriguingly, AKR1A1 depletion induced phosphorylation of p53 at serine 15 and G 2/M transition in response to irradiation. We further found that AKR1A1 interacted with p53 and this interaction was dramatically increased in the irradiated radioresistant cells compared with the control cells. AKR1A1 expression also regulated p53 stability in ...Continue Reading

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Citations

Feb 24, 2016·Cancer Biology & Therapy·Hong Shik YunSang-Gu Hwang
Sep 21, 2013·Biochemical and Biophysical Research Communications·Joong Won MinJae-Sung Kim
May 5, 2017·International Journal of Molecular Sciences·Sumadi Lukman AnwarUlrich Lehmann
Nov 9, 2016·Oncotarget·Jiang-Tao Zhong, Shui-Hong Zhou
Feb 20, 2018·Experimental and Therapeutic Medicine·Qiong ZhangKun Yuan
Jun 3, 2021·Metabolites·Junichi FujiiMotoko Takahashi

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