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Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition
- Source :
- Oncogene, Oncogene, Nature Publishing Group, 2007, 26 (53), pp.7445-56. ⟨10.1038/sj.onc.1210546⟩
- Publication Year :
- 2007
- Publisher :
- HAL CCSD, 2007.
-
Abstract
- International audience; Carcinoma progression is associated with the loss of epithelial features, and the acquisition of mesenchymal characteristics and invasive properties by tumour cells. The loss of cell-cell contacts may be the first step of the epithelium mesenchyme transition (EMT) and involves the functional inactivation of the cell-cell adhesion molecule E-cadherin. Repression of E-cadherin expression by the transcription factor Snail is a central event during the loss of epithelial phenotype. Akt kinase activation is frequent in human carcinomas, and Akt regulates various cellular mechanisms including EMT. Here, we show that Snail activation and consequent repression of E-cadherin may depend on AKT-mediated nuclear factor-kappaB (NF-kappaB) activation, and that NF-kappaB induces Snail expression. Expression of the NF-kappaB subunit p65 is sufficient for EMT induction, validating this signalling module during EMT. NF-kappaB pathway activation is associated with tumour progression and metastasis of several human tumour types; E-cadherin acts as a metastasis suppressor protein. Thus, this signalling and transcriptional network linking AKT, NF-kappaB, Snail and E-cadherin during EMT is a potential target for antimetastatic therapeutics.
- Subjects :
- MESH: Signal Transduction
Cancer Research
Transcription, Genetic
Snail
medicine.disease_cause
Epithelium
MESH: Cadherins
Mesoderm
0302 clinical medicine
MESH: Transcription Factor RelA
MESH: Up-Regulation
MESH: Animals
Promoter Regions, Genetic
0303 health sciences
MESH: Mesoderm
biology
MESH: Carcinoma, Squamous Cell
MESH: Transcription Factors
Cadherins
Cell biology
Up-Regulation
MESH: Urinary Bladder Neoplasms
MESH: Promoter Regions (Genetics)
medicine.anatomical_structure
MESH: Repressor Proteins
030220 oncology & carcinogenesis
Carcinoma, Squamous Cell
Disease Progression
MESH: Disease Progression
Signal transduction
Metastasis Suppressor Protein
Signal Transduction
MESH: Cell Line, Tumor
MESH: Rats
Mesenchyme
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Transfection
03 medical and health sciences
biology.animal
Cell Line, Tumor
MESH: Homeodomain Proteins
Genetics
medicine
Animals
Molecular Biology
Protein kinase B
Transcription factor
030304 developmental biology
Zinc Finger E-box Binding Homeobox 2
Homeodomain Proteins
MESH: Proto-Oncogene Proteins c-akt
MESH: Transcription, Genetic
MESH: Transfection
Transcription Factor RelA
Rats
Repressor Proteins
MESH: Epithelium
Urinary Bladder Neoplasms
Immunology
Snail Family Transcription Factors
Carcinogenesis
Proto-Oncogene Proteins c-akt
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 09509232 and 14765594
- Database :
- OpenAIRE
- Journal :
- Oncogene, Oncogene, Nature Publishing Group, 2007, 26 (53), pp.7445-56. ⟨10.1038/sj.onc.1210546⟩
- Accession number :
- edsair.doi.dedup.....23489da6d8afbf91e474fc75128a4ef3