Targeting SGK1 enhances the efficacy of radiotherapy in locally advanced rectal cancer.

Abstract	Radiotherapy (RT) is a key component of neoadjuvant chemoradiotherapy to treat locally advanced rectal cancer (LARC). However, the therapeutic effect is limited due to radioresistance. Investigating the biomarkers of radioresistance might assist in the development of more effective therapeutic strategies for LARC.In this study, we investigated the different gene expressions in tumor samples from 110 patients using transcriptome analysis and immunohistochemistry (IHC), and identified serum- and glucocorticoid-regulated kinase 1 (SGK1) as a modulator of LARC radioresistance. We evaluated the impact of genetic and pharmacologic inhibition of the gene associated with radioresistance in vitro and in vivo. We found that the expression of SGK1 was upregulated in non-pathological complete response (non-pCR) patients. A high SGK1 expression was associated with radioresistance, whereas the genetic or pharmacologic inhibition of SGK1 expression reduced the radioresistance. We found that activate transcription factor 3 (ATF3) is a regulator of SGK1 in radioresistance.In conclusion, our findings indicate that SGK1 is a key player in LARC radioresistance, and drives radioresistance in an ATF3 dependent manner, which provides insights for future radio-sensitizer design.
Authors	Chunlian Zhou, Weiwei Xiao, Ting Jiang, Zhiwei Guo, Min Li, Hui Chang, Yingsong Wu, Minshan Chen, Mude Shi, Weiwen Xu, Yuanhong Gao
Journal	Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 125 Pg. 109954 (May 2020) ISSN: 1950-6007 [Electronic] France
PMID	32036218 (Publication Type: Journal Article)
Copyright	Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Chemical References	Immediate-Early Proteins Protein Serine-Threonine Kinases serum-glucocorticoid regulated kinase
Topics	Adult Aged Animals Cell Line, Tumor Female Gene Expression Regulation, Neoplastic Humans Immediate-Early Proteins (genetics, metabolism) Male Mice Mice, Nude Middle Aged Neoplasms, Experimental Protein Serine-Threonine Kinases (genetics, metabolism) Rectal Neoplasms (drug therapy, radiotherapy)

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