FBXL5 Inhibits Metastasis of Gastric Cancer Through Suppressing Snail1

Background/Aims: The Snail family of transcription factors controls epithelial to mesenchymal transition (EMT), a process associated with tumorigenesis originated from epithelial cells. Snail1 is a member from Snail family and upregulation of Snail1 has been detected in gastric cancer (GC), suggesti...

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Main Authors: Weidong Wu, Honghua Ding, Jun Cao, Weihao Zhang
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2015-03-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/373988
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author Weidong Wu
Honghua Ding
Jun Cao
Weihao Zhang
author_facet Weidong Wu
Honghua Ding
Jun Cao
Weihao Zhang
author_sort Weidong Wu
collection DOAJ
description Background/Aims: The Snail family of transcription factors controls epithelial to mesenchymal transition (EMT), a process associated with tumorigenesis originated from epithelial cells. Snail1 is a member from Snail family and upregulation of Snail1 has been detected in gastric cancer (GC), suggesting a potential role of Snail1 in GC metastasis. We have recently reported that FBXL5 regulates cortactin by inducing its ubiquitylation and subsequent proteasomal degradation, resulting in inhibition of metastasis of GC. However, a role of FBXL4 in regulation of other EMT-associated proteins is not unknown. Methods: The levels of FBXL5 and Snail1 as well as their relationship were determined in GC specimen. Co-immunoprecipitation (IP) was performed to detect the interaction between Snail1 and FBXL5 in GC cells. The effects on Snail1 by FBXL5 were examined by overexpression of depletion of FBXL5 in GC cells. The invasiveness of the FBXL5-modified GC cells was examined in both scratch wound healing assay and transwell matrix penetration assay. Results: FBXL5 also physiologically interacted with Snail1. FBXL5 inhibited Snail1 to suppress GC cell invasiveness. Conclusion: FBXL5 negatively regulates several EMT-enhancing factors. FBXL5 is an attractive novel target for inhibiting invasion and metastasis of GC cells.
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spelling doaj.art-5ae33ce32d4f46acbaa441c5455789b62022-12-21T19:13:26ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-03-013551764177210.1159/000373988373988FBXL5 Inhibits Metastasis of Gastric Cancer Through Suppressing Snail1Weidong WuHonghua DingJun CaoWeihao ZhangBackground/Aims: The Snail family of transcription factors controls epithelial to mesenchymal transition (EMT), a process associated with tumorigenesis originated from epithelial cells. Snail1 is a member from Snail family and upregulation of Snail1 has been detected in gastric cancer (GC), suggesting a potential role of Snail1 in GC metastasis. We have recently reported that FBXL5 regulates cortactin by inducing its ubiquitylation and subsequent proteasomal degradation, resulting in inhibition of metastasis of GC. However, a role of FBXL4 in regulation of other EMT-associated proteins is not unknown. Methods: The levels of FBXL5 and Snail1 as well as their relationship were determined in GC specimen. Co-immunoprecipitation (IP) was performed to detect the interaction between Snail1 and FBXL5 in GC cells. The effects on Snail1 by FBXL5 were examined by overexpression of depletion of FBXL5 in GC cells. The invasiveness of the FBXL5-modified GC cells was examined in both scratch wound healing assay and transwell matrix penetration assay. Results: FBXL5 also physiologically interacted with Snail1. FBXL5 inhibited Snail1 to suppress GC cell invasiveness. Conclusion: FBXL5 negatively regulates several EMT-enhancing factors. FBXL5 is an attractive novel target for inhibiting invasion and metastasis of GC cells.http://www.karger.com/Article/FullText/373988FBXL5Gastric cancerSnail1Cancer invasionMetastasis
spellingShingle Weidong Wu
Honghua Ding
Jun Cao
Weihao Zhang
FBXL5 Inhibits Metastasis of Gastric Cancer Through Suppressing Snail1
Cellular Physiology and Biochemistry
FBXL5
Gastric cancer
Snail1
Cancer invasion
Metastasis
title FBXL5 Inhibits Metastasis of Gastric Cancer Through Suppressing Snail1
title_full FBXL5 Inhibits Metastasis of Gastric Cancer Through Suppressing Snail1
title_fullStr FBXL5 Inhibits Metastasis of Gastric Cancer Through Suppressing Snail1
title_full_unstemmed FBXL5 Inhibits Metastasis of Gastric Cancer Through Suppressing Snail1
title_short FBXL5 Inhibits Metastasis of Gastric Cancer Through Suppressing Snail1
title_sort fbxl5 inhibits metastasis of gastric cancer through suppressing snail1
topic FBXL5
Gastric cancer
Snail1
Cancer invasion
Metastasis
url http://www.karger.com/Article/FullText/373988
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