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Therapeutic inhibition of SGK1 suppresses colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its ro...

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Autores principales: Liang, Xuchun, Lan, Chunling, Jiao, Guanming, Fu, Wencheng, Long, Xuesha, An, Yu, Wang, Kejin, Zhou, Jinzhe, Chen, Ting, Li, Yongqin, Xu, Jiahong, Huang, Qi, Xu, Bin, Xiao, Junjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704191/
https://www.ncbi.nlm.nih.gov/pubmed/29170478
http://dx.doi.org/10.1038/emm.2017.184
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author Liang, Xuchun
Lan, Chunling
Jiao, Guanming
Fu, Wencheng
Long, Xuesha
An, Yu
Wang, Kejin
Zhou, Jinzhe
Chen, Ting
Li, Yongqin
Xu, Jiahong
Huang, Qi
Xu, Bin
Xiao, Junjie
author_facet Liang, Xuchun
Lan, Chunling
Jiao, Guanming
Fu, Wencheng
Long, Xuesha
An, Yu
Wang, Kejin
Zhou, Jinzhe
Chen, Ting
Li, Yongqin
Xu, Jiahong
Huang, Qi
Xu, Bin
Xiao, Junjie
author_sort Liang, Xuchun
collection PubMed
description Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.
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spelling pubmed-57041912017-12-07 Therapeutic inhibition of SGK1 suppresses colorectal cancer Liang, Xuchun Lan, Chunling Jiao, Guanming Fu, Wencheng Long, Xuesha An, Yu Wang, Kejin Zhou, Jinzhe Chen, Ting Li, Yongqin Xu, Jiahong Huang, Qi Xu, Bin Xiao, Junjie Exp Mol Med Original Article Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC. Nature Publishing Group 2017-11 2017-11-24 /pmc/articles/PMC5704191/ /pubmed/29170478 http://dx.doi.org/10.1038/emm.2017.184 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Article
Liang, Xuchun
Lan, Chunling
Jiao, Guanming
Fu, Wencheng
Long, Xuesha
An, Yu
Wang, Kejin
Zhou, Jinzhe
Chen, Ting
Li, Yongqin
Xu, Jiahong
Huang, Qi
Xu, Bin
Xiao, Junjie
Therapeutic inhibition of SGK1 suppresses colorectal cancer
title Therapeutic inhibition of SGK1 suppresses colorectal cancer
title_full Therapeutic inhibition of SGK1 suppresses colorectal cancer
title_fullStr Therapeutic inhibition of SGK1 suppresses colorectal cancer
title_full_unstemmed Therapeutic inhibition of SGK1 suppresses colorectal cancer
title_short Therapeutic inhibition of SGK1 suppresses colorectal cancer
title_sort therapeutic inhibition of sgk1 suppresses colorectal cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704191/
https://www.ncbi.nlm.nih.gov/pubmed/29170478
http://dx.doi.org/10.1038/emm.2017.184
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