Targeting SGK1 enhances the efficacy of radiotherapy in locally advanced rectal cancer
| Autor: | Yuanhong Gao, Minshan Chen, Mude Shi, Ting Jiang, Min Li, Weiwei Xiao, Weiwen Xu, Zhi-Wei Guo, Hui Chang, Chun-Lian Zhou, Ying-Song Wu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male Colorectal cancer medicine.medical_treatment Regulator Mice Nude RM1-950 Protein Serine-Threonine Kinases Immediate-Early Proteins Transcriptome 03 medical and health sciences Mice 0302 clinical medicine In vivo Radioresistance Cell Line Tumor medicine Animals Humans ATF3 SGK1 Locally advanced rectal cancer Aged Pharmacology Radiotherapy business.industry Rectal Neoplasms urogenital system General Medicine Neoplasms Experimental Middle Aged medicine.disease Radiation therapy Gene Expression Regulation Neoplastic Neoadjuvant chemoradiotherapy 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Female Therapeutics. Pharmacology business |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 125, Iss, Pp 109954-(2020) |
| ISSN: | 0753-3322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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