Deregulation of FoxM1b leads to tumour metastasis

130Citations
Citations of this article
71Readers
Mendeley users who have this article in their library.

This article is free to access.

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. Copyright © 2011 EMBO Molecular Medicine.

Author supplied keywords

References Powered by Scopus

Epithelial-Mesenchymal Transitions in Development and Disease

8318Citations
N/AReaders
Get full text

The basics of epithelial-mesenchymal transition

8291Citations
N/AReaders
Get full text

Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor

5652Citations
N/AReaders
Get full text

Cited by Powered by Scopus

FOXM1: From cancer initiation to progression and treatment

336Citations
N/AReaders
Get full text

FoxM1: A master regulator of tumor metastasis

256Citations
N/AReaders
Get full text

Lysyl oxidase, extracellular matrix remodeling and cancer metastasis

192Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Park, H. J., Gusarova, G., Wang, Z., Carr, J. R., Li, J., Kim, K. H., … Raychaudhuri, P. (2011). Deregulation of FoxM1b leads to tumour metastasis. EMBO Molecular Medicine, 3(1), 21–34. https://doi.org/10.1002/emmm.201000107

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 35

66%

Researcher 14

26%

Professor / Associate Prof. 4

8%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 27

50%

Biochemistry, Genetics and Molecular Bi... 17

31%

Medicine and Dentistry 9

17%

Engineering 1

2%

Save time finding and organizing research with Mendeley

Sign up for free