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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Bibliographic Details
Published inOncogene Vol. 38; no. 17; pp. 3248 - 3260
Main Authors Jang, Donghwan, Kwon, Hayeong, Choi, Moonjeong, Lee, Jaewoong, Pak, Yunbae
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.04.2019
Nature Publishing Group
Subjects
13/1
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13/89
14/19
14/63
38/39
38/70
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38/90
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Apoptosis
Cancer cells
Cancer metastasis
Care and treatment
Cell Biology
Cellular signal transduction
Development and progression
Enzymes
Genetic aspects
Genetic research
Human Genetics
Internal Medicine
Medicine
Medicine & Public Health
Mesenchyme
Metastases
Metastasis
Mitogens
Novels
Nuclear transport
Oncology
Post-translation
Prostate cancer
Proteasomes
Stem cells
SUMO protein
Ubiquitin
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Summary: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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ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-018-0641-1