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Sumoylation of Flotillin-1 promotes EMT in metastatic prostate cancer by suppressing Snail degradation

Flotillin-1 (Flot-1) has been shown to regulate cancer progression, but the regulatory role of post-translational modifications of Flot-1 on cancers remains elusive. Herein, we show that up-regulated E2 conjugating enzyme UBC9 sumoylates Flot-1 at Lys-51 and Lys-195 with small ubiquitin-like modifie...

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Autores principales: Jang, Donghwan, Kwon, Hayeong, Choi, Moonjeong, Lee, Jaewoong, Pak, Yunbae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756018/
https://www.ncbi.nlm.nih.gov/pubmed/30631151
http://dx.doi.org/10.1038/s41388-018-0641-1
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author Jang, Donghwan
Kwon, Hayeong
Choi, Moonjeong
Lee, Jaewoong
Pak, Yunbae
author_facet Jang, Donghwan
Kwon, Hayeong
Choi, Moonjeong
Lee, Jaewoong
Pak, Yunbae
author_sort Jang, Donghwan
collection PubMed
description Flotillin-1 (Flot-1) has been shown to regulate cancer progression, but the regulatory role of post-translational modifications of Flot-1 on cancers remains elusive. Herein, we show that up-regulated E2 conjugating enzyme UBC9 sumoylates Flot-1 at Lys-51 and Lys-195 with small ubiquitin-like modifier (SUMO)-2/3 modification in metastatic prostate cancer. Mitogen induced the sumoylation and nuclear translocation of Flot-1. The nuclear-targeted Flot-1 physically interacted with Snail, and inhibited Snail degradation through the proteasome in a sumoylation-dependent manner, thereby promoting epithelial-to-mesenchymal transition (EMT). Sumoylation of Flot-1 by up-regulated UBC9 in human metastatic prostate cancer tissues and prostate cancer cells with high metastatic potential positively correlated with the stabilization of Snail and the induction of Snail-mediated EMT genes in the metastatic prostate cancer. Our study reveals a new mechanism of sumoylated Flot-1-mediating Snail stabilization, and identifies a novel sumoylated Flot-1-Snail signaling axis in EMT of metastatic prostate cancer.
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spelling pubmed-67560182019-09-24 Sumoylation of Flotillin-1 promotes EMT in metastatic prostate cancer by suppressing Snail degradation Jang, Donghwan Kwon, Hayeong Choi, Moonjeong Lee, Jaewoong Pak, Yunbae Oncogene Article Flotillin-1 (Flot-1) has been shown to regulate cancer progression, but the regulatory role of post-translational modifications of Flot-1 on cancers remains elusive. Herein, we show that up-regulated E2 conjugating enzyme UBC9 sumoylates Flot-1 at Lys-51 and Lys-195 with small ubiquitin-like modifier (SUMO)-2/3 modification in metastatic prostate cancer. Mitogen induced the sumoylation and nuclear translocation of Flot-1. The nuclear-targeted Flot-1 physically interacted with Snail, and inhibited Snail degradation through the proteasome in a sumoylation-dependent manner, thereby promoting epithelial-to-mesenchymal transition (EMT). Sumoylation of Flot-1 by up-regulated UBC9 in human metastatic prostate cancer tissues and prostate cancer cells with high metastatic potential positively correlated with the stabilization of Snail and the induction of Snail-mediated EMT genes in the metastatic prostate cancer. Our study reveals a new mechanism of sumoylated Flot-1-mediating Snail stabilization, and identifies a novel sumoylated Flot-1-Snail signaling axis in EMT of metastatic prostate cancer. Nature Publishing Group UK 2019-01-10 2019 /pmc/articles/PMC6756018/ /pubmed/30631151 http://dx.doi.org/10.1038/s41388-018-0641-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jang, Donghwan
Kwon, Hayeong
Choi, Moonjeong
Lee, Jaewoong
Pak, Yunbae
Sumoylation of Flotillin-1 promotes EMT in metastatic prostate cancer by suppressing Snail degradation
title Sumoylation of Flotillin-1 promotes EMT in metastatic prostate cancer by suppressing Snail degradation
title_full Sumoylation of Flotillin-1 promotes EMT in metastatic prostate cancer by suppressing Snail degradation
title_fullStr Sumoylation of Flotillin-1 promotes EMT in metastatic prostate cancer by suppressing Snail degradation
title_full_unstemmed Sumoylation of Flotillin-1 promotes EMT in metastatic prostate cancer by suppressing Snail degradation
title_short Sumoylation of Flotillin-1 promotes EMT in metastatic prostate cancer by suppressing Snail degradation
title_sort sumoylation of flotillin-1 promotes emt in metastatic prostate cancer by suppressing snail degradation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756018/
https://www.ncbi.nlm.nih.gov/pubmed/30631151
http://dx.doi.org/10.1038/s41388-018-0641-1
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