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SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT

BACKGROUND: Despite SGK1 has been identified and characterized as a tumor-promoting gene, the functions and underlying mechanisms of SGK1 involved in metastasis regulation have not yet been investigated in cancer. METHODS: We investigated the cellular responses to GSK650394 treatment and SGK1 silenc...

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Autores principales: Liu, Weiwei, Wang, Xuchu, Wang, Yiyun, Dai, Yibei, Xie, Yiyi, Ping, Ying, Yin, Binbin, Yu, Pan, Liu, Zhenping, Duan, Xiuzhi, Liao, Zhaoping, Chen, Yuhua, Liu, Chunhua, Li, Xiang, Tao, Zhihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879613/
https://www.ncbi.nlm.nih.gov/pubmed/29609629
http://dx.doi.org/10.1186/s13046-018-0743-1
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author Liu, Weiwei
Wang, Xuchu
Wang, Yiyun
Dai, Yibei
Xie, Yiyi
Ping, Ying
Yin, Binbin
Yu, Pan
Liu, Zhenping
Duan, Xiuzhi
Liao, Zhaoping
Chen, Yuhua
Liu, Chunhua
Li, Xiang
Tao, Zhihua
author_facet Liu, Weiwei
Wang, Xuchu
Wang, Yiyun
Dai, Yibei
Xie, Yiyi
Ping, Ying
Yin, Binbin
Yu, Pan
Liu, Zhenping
Duan, Xiuzhi
Liao, Zhaoping
Chen, Yuhua
Liu, Chunhua
Li, Xiang
Tao, Zhihua
author_sort Liu, Weiwei
collection PubMed
description BACKGROUND: Despite SGK1 has been identified and characterized as a tumor-promoting gene, the functions and underlying mechanisms of SGK1 involved in metastasis regulation have not yet been investigated in cancer. METHODS: We investigated the cellular responses to GSK650394 treatment and SGK1 silencing (or overexpression) in human prostate cancer (PCa) cell lines and PC3 xenografts by wound healing assay, migration and invasion assay, western blotting, immunofluorescence and immunohistochemistry. RESULTS: In the present study, we found that SGK1 expression positively correlates with human prostate cancer (PCa) progression and metastasis. We show that SGK1 inhibition significantly attenuates EMT and metastasis both in vitro and in vivo, whereas overexpression of SGK1 dramaticlly promoted the invasion and migration of PCa cells. Our further results suggest that SGK1 inhibition induced antimetastatic effects, at least partially via autophagy-mediated repression of EMT through the downregulation of Snail. Moreover, ectopic expression of SGK1 obviously attenuated the GSK650394-induced autophagy and antimetastatic effects. What’s more, dual inhibition of mTOR and SGK1 enhances autophagy and leads to synergistic antimetastatic effects on PCa cells. CONCLUSIONS: Taken together, this study unveils a novel mechanism in which SGK1 functions as a tumor metastasis-promoting gene and highlights how co-targeting SGK1 and autophagy restrains cancer progression due to the amplified antimetastatic effects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0743-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-58796132018-04-04 SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT Liu, Weiwei Wang, Xuchu Wang, Yiyun Dai, Yibei Xie, Yiyi Ping, Ying Yin, Binbin Yu, Pan Liu, Zhenping Duan, Xiuzhi Liao, Zhaoping Chen, Yuhua Liu, Chunhua Li, Xiang Tao, Zhihua J Exp Clin Cancer Res Research BACKGROUND: Despite SGK1 has been identified and characterized as a tumor-promoting gene, the functions and underlying mechanisms of SGK1 involved in metastasis regulation have not yet been investigated in cancer. METHODS: We investigated the cellular responses to GSK650394 treatment and SGK1 silencing (or overexpression) in human prostate cancer (PCa) cell lines and PC3 xenografts by wound healing assay, migration and invasion assay, western blotting, immunofluorescence and immunohistochemistry. RESULTS: In the present study, we found that SGK1 expression positively correlates with human prostate cancer (PCa) progression and metastasis. We show that SGK1 inhibition significantly attenuates EMT and metastasis both in vitro and in vivo, whereas overexpression of SGK1 dramaticlly promoted the invasion and migration of PCa cells. Our further results suggest that SGK1 inhibition induced antimetastatic effects, at least partially via autophagy-mediated repression of EMT through the downregulation of Snail. Moreover, ectopic expression of SGK1 obviously attenuated the GSK650394-induced autophagy and antimetastatic effects. What’s more, dual inhibition of mTOR and SGK1 enhances autophagy and leads to synergistic antimetastatic effects on PCa cells. CONCLUSIONS: Taken together, this study unveils a novel mechanism in which SGK1 functions as a tumor metastasis-promoting gene and highlights how co-targeting SGK1 and autophagy restrains cancer progression due to the amplified antimetastatic effects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0743-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-02 /pmc/articles/PMC5879613/ /pubmed/29609629 http://dx.doi.org/10.1186/s13046-018-0743-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Liu, Weiwei
Wang, Xuchu
Wang, Yiyun
Dai, Yibei
Xie, Yiyi
Ping, Ying
Yin, Binbin
Yu, Pan
Liu, Zhenping
Duan, Xiuzhi
Liao, Zhaoping
Chen, Yuhua
Liu, Chunhua
Li, Xiang
Tao, Zhihua
SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT
title SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT
title_full SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT
title_fullStr SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT
title_full_unstemmed SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT
title_short SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT
title_sort sgk1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing emt
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879613/
https://www.ncbi.nlm.nih.gov/pubmed/29609629
http://dx.doi.org/10.1186/s13046-018-0743-1
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