Publication date: September 2017
Source:Neoplasia, Volume 19, Issue 9
Author(s): Junlan Zhu, Yang Li, Caiyi Chen, Jiugao Ma, Wenrui Sun, Zhongxian Tian, Jingxia Li, Jiheng Xu, Claire S Liu, Dongyun Zhang, Chuanshu Huang, Haishan Huang
BACKGROUND: Since invasive bladder cancer (BC) is one of the most lethal urological malignant tumors worldwide, understanding the molecular mechanisms that trigger the migration, invasion, and metastasis of BC has great significance in reducing the mortality of this disease. Although RelA/p65, a member of the NF-kappa B transcription factor family, has been reported to be upregulated in human BCs, its regulation of BC motility and mechanisms have not been explored yet. METHODS: NF-κBp65 expression was evaluated in N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)–induced high invasive BCs by immunohistochemistry staining and in human BC cell lines demonstrated by Western Blot. The effects of NF-κBp65 knockdown on BC cell migration and invasion, as well as its regulated RhoGDIα and FBW7, were also evaluated in T24T cells by using loss- and gain-function approaches. Moreover, the interaction of FBW7 with RhoGDIα was determined with immunoprecipitation assay, while critical role of ubiquitination of RhoGDIα by FBW7 was also demonstrated in the studies. RESULTS: p65 protein was remarkably upregulated in the BBN-induced high invasive BCs and in human BC cell lines. We also observed that p65 overexpression promoted BC cell migration by inhibiting RhoGDIα expression. The regulatory effect of p65 on RhoGDIα expression is mediated by its upregulation of FBW7, which specifically interacted with RhoGDIα and promoted RhoGDIα ubiquitination and degradation. Mechanistic studies revealed that p65 stabilizing the E3 ligase FBW7 protein was mediated by its attenuating pten mRNA transcription. CONCLUSIONS: We demonstrate that p65 overexpression inhibits pten mRNA transcription, which stabilizes the protein expression of ubiquitin E3 ligase FBW7, in turn increasing the ubiquitination and degradation of RhoGDIα protein and finally promoting human BC migration. The novel identification of p65/PTEN/FBW7/RhoGDIα axis provides a significant insight into understanding the nature of BC migration, further offering a new theoretical support for cancer therapy.
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Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com
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Τρίτη 1 Αυγούστου 2017
NF-κB p65 Overexpression Promotes Bladder Cancer Cell Migration via FBW7-Mediated Degradation of RhoGDIα Protein
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- Neural Evidence for Non-conscious Working Memory
- Transcription Factors Sp8 and Sp9 Coordinately Reg...
- Efficacy of a novel swallowing exercise program fo...
- Symptom burden and patient characteristics: Associ...
- Efficacy of a novel swallowing exercise program fo...
- Symptom burden and patient characteristics: Associ...
- The Mediator Complex: At the Nexus of RNA Polymera...
- College student with actigraphy performed during f...
- Sleep Phenotypes in Infants and Toddlers with Neur...
- Reduced P300 amplitude during a visuospatial atten...
- Correlation Between the Epworth Sleepiness Scale a...
- Relapse insomnia increases greater risk of anxiety...
- A preliminary examination of gut microbiota, sleep...
- A comparison of the tongue-in-groove and columella...
- CONTENTS 1
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- Thyroid Transcription Factor-1 promotes lymph node...
- Exploration of the pathways and interaction networ...
- Evaluation of expression of genes CADM1, TWIST1 an...
- Optical Loupes: A Useful Tool for the Oncall Otorh...
- Optical Loupes: A Useful Tool for the Oncall Otorh...
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- Expansion of cytotoxic CD56bright NK cells during ...
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- Retropharyngeal abscess as a result of hyaluronic ...
- Increasing positive attitudes toward individuals w...
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- Zika virus infection as a trigger of atopic dermat...
- Increased malignancy incidence in IgE deficient pa...
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