Targeting SGK1 enhances the efficacy of radiotherapy in locally advanced rectal cancer - 14/03/20
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Graphical abstract |
Highlights |
• | Overexpression of SGK1 in LARC correlated with radioresistance. |
• | Pharmacologic inhibition of SGK1 reduced the radioresistance of LARC in vitro and in vivo. |
• | SGK1 is a key player in LARC radioresistance and drives radioresistance in an ATF3 dependent manner. |
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.
El texto completo de este artículo está disponible en PDF.Keywords : SGK1, Radiotherapy, Locally advanced rectal cancer, ATF3, Neoadjuvant chemoradiotherapy
Esquema
Vol 125
Artículo 109954- mai 2020 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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