Back to Search
Start Over
Deregulation of FoxM1b leads to tumour metastasis
- Source :
- EMBO Molecular Medicine
- Publication Year :
- 2010
- Publisher :
- EMBO, 2010.
-
Abstract
- The forkhead box M1b (FoxM1b) transcription factor is over-expressed in human cancers, and its expression often correlates with poor prognosis. Previously, using conditional knockout strains, we showed that FoxM1b is essential for hepatocellular carcinoma (HCC) development. However, over-expression of FoxM1b had only marginal effects on HCC progression. Here we investigated the effect of FoxM1b expression in the absence of its inhibitor Arf. We show that transgenic expression of FoxM1b in an Arf-null background drives hepatic fibrosis and metastasis of HCC. We identify novel mechanisms of FoxM1b that are involved in epithelial–mesenchymal transition, cell motility, invasion and a pre-metastatic niche formation. FoxM1b activates the Akt-Snail1 pathway and stimulates expression of Stathmin, lysyl oxidase, lysyl oxidase like-2 and several other genes involved in metastasis. Furthermore, we show that an Arf-derived peptide, which inhibits FoxM1b, impedes metastasis of the FoxM1b-expressing HCC cells. The observations indicate that FoxM1b is a potent activator of tumour metastasis and that the Arf-mediated inhibition of FoxM1b is a critical mechanism for suppression of tumour metastasis.
- Subjects :
- Liver Cirrhosis
Carcinoma, Hepatocellular
Epithelial-Mesenchymal Transition
Mice, Transgenic
Stathmin
Lysyl oxidase
Metastasis
Protein-Lysine 6-Oxidase
Mice
03 medical and health sciences
0302 clinical medicine
Conditional gene knockout
medicine
Carcinoma
Animals
Humans
metastasis
Epithelial–mesenchymal transition
Neoplasm Metastasis
Transcription factor
Research Articles
030304 developmental biology
0303 health sciences
biology
ADP-Ribosylation Factors
Forkhead Box Protein M1
Liver Neoplasms
Arf
Forkhead Transcription Factors
medicine.disease
3. Good health
030220 oncology & carcinogenesis
FoxM1
biology.protein
Cancer research
FOXM1
Molecular Medicine
Snail Family Transcription Factors
Proto-Oncogene Proteins c-akt
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 17574684 and 17574676
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- EMBO Molecular Medicine
- Accession number :
- edsair.doi.dedup.....120a26727439f25bb56202aca71dfac3