The F‐box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin‐mediated degradation of Snail

The F‐box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin‐mediated degradation of Snail

Expression of the F‐box protein FBXO11 has been shown to be down‐regulated in various tumors, but its role in hepatocellular carcinoma (HCC) progression remains unclear. Here, we examined the role of FBXO11 in HCC cell stemness. We report that FBXO11 expression is significantly decreased in HCC cell...

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Bibliographic Details
Main Authors: Lijiang Shao, Xuehui Zhang, Qi Yao
Format: Article
Language:English
Published: Wiley 2020-09-01
Series:FEBS Open Bio
Subjects:
ALDH1
FBXO11
hepatocellular carcinoma
Snail
stemness
Online Access:https://doi.org/10.1002/2211-5463.12933
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spelling doaj-a113d83ec1064baabaafe6f9fabc7cac2020-11-25T02:06:06ZengWileyFEBS Open Bio2211-54632020-09-011091810182010.1002/2211-5463.12933The F‐box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin‐mediated degradation of SnailLijiang Shao0Xuehui Zhang1Qi Yao2Department of Emergency Ningbo First Hospital Ningbo ChinaDepartment of Emergency Ningbo First Hospital Ningbo ChinaDepartment of Geriatric Medicine Ningbo First Hospital Ningbo ChinaExpression of the F‐box protein FBXO11 has been shown to be down‐regulated in various tumors, but its role in hepatocellular carcinoma (HCC) progression remains unclear. Here, we examined the role of FBXO11 in HCC cell stemness. We report that FBXO11 expression is significantly decreased in HCC cells, and overexpression of FBXO11 decreased the expression of HCC stemness markers, ALDH1 activity and sphere‐forming ability. In addition, overexpression of FBXO11 reduced the migration ability and epithelial‐mesenchymal transition of HCC cells. Mechanistically, overexpression of FBXO11 decreased the protein level, but not mRNA level, of Snail by directly interacting with Snail and promoting Snail degradation through the ubiquitin‐proteasome system. Overexpression of Snail rescued the inhibitory effect of FBXO11 overexpression on HCC cell stemness. This study reveals the existence of a novel FBXO11/Snail regulatory axis that is necessary for HCC cell stemness.https://doi.org/10.1002/2211-5463.12933ALDH1FBXO11hepatocellular carcinomaSnailstemness
collection DOAJ
language English
format Article
sources DOAJ
author Lijiang Shao
Xuehui Zhang
Qi Yao
spellingShingle Lijiang Shao
Xuehui Zhang
Qi Yao
The F‐box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin‐mediated degradation of Snail
FEBS Open Bio
ALDH1
FBXO11
hepatocellular carcinoma
Snail
stemness
author_facet Lijiang Shao
Xuehui Zhang
Qi Yao
author_sort Lijiang Shao
title The F‐box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin‐mediated degradation of Snail
title_short The F‐box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin‐mediated degradation of Snail
title_full The F‐box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin‐mediated degradation of Snail
title_fullStr The F‐box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin‐mediated degradation of Snail
title_full_unstemmed The F‐box protein FBXO11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin‐mediated degradation of Snail
title_sort f‐box protein fbxo11 restrains hepatocellular carcinoma stemness via promotion of ubiquitin‐mediated degradation of snail
publisher Wiley
series FEBS Open Bio
issn 2211-5463
publishDate 2020-09-01
description Expression of the F‐box protein FBXO11 has been shown to be down‐regulated in various tumors, but its role in hepatocellular carcinoma (HCC) progression remains unclear. Here, we examined the role of FBXO11 in HCC cell stemness. We report that FBXO11 expression is significantly decreased in HCC cells, and overexpression of FBXO11 decreased the expression of HCC stemness markers, ALDH1 activity and sphere‐forming ability. In addition, overexpression of FBXO11 reduced the migration ability and epithelial‐mesenchymal transition of HCC cells. Mechanistically, overexpression of FBXO11 decreased the protein level, but not mRNA level, of Snail by directly interacting with Snail and promoting Snail degradation through the ubiquitin‐proteasome system. Overexpression of Snail rescued the inhibitory effect of FBXO11 overexpression on HCC cell stemness. This study reveals the existence of a novel FBXO11/Snail regulatory axis that is necessary for HCC cell stemness.
topic ALDH1
FBXO11
hepatocellular carcinoma
Snail
stemness
url https://doi.org/10.1002/2211-5463.12933
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