Article: Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers

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Title	Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers
Authors	Jiang, L1 4 Siu, MKY1 Wong, OGW1 Tam, KF1 Lam, EWF2 Ngan, HYS1 Le, XF3 Wong, ESY1 Chan, HY1 Cheung, ANY1
Issue Date	2010
Publisher	BioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
Citation	Molecular Cancer, 2010, v. 9 [How to Cite?] DOI: http://dx.doi.org/10.1186/1476-4598-9-318
Abstract	Background: FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) is a member of the POK (POZ and Kruppel) family of transcription factors and play important roles in cellular differentiation and oncogenesis. Recent evidence suggests that FBI-1 is expressed at high levels in a subset of human lymphomas and some epithelial solid tumors. However, the function of FBI-1 in human ovarian cancers remains elusive.Results: In this study, we investigated the role of FBI-1 in human ovarian cancers, in particularly, its function in cancer cell invasion via modulating membrane type 1-matrix metalloproteinase (MT1-MMP). Significantly higher FBI-1 protein and mRNA expression levels were demonstrated in ovarian cancers samples and cell lines compared with borderline tumors and benign cystadenomas. Increased FBI-1 mRNA expression was correlated significantly with gene amplification (P = 0.037). Moreover, higher FBI-1 expression was found in metastatic foci (P = 0.036) and malignant ascites (P = 0.021), and was significantly associated with advanced stage (P = 0.012), shorter overall survival (P = 0.032) and disease-free survival (P = 0.016). In vitro, overexpressed FBI-1 significantly enhanced cell migration and invasion both in OVCA 420 and SKOV-3 ovarian carcinoma cells, irrespective of p53 status, accompanied with elevated expression of MT1-MMP, but not MMP-2 or TIMP-2. Moreover, knockdown of MT1-MMP abolished FBI-1-mediated cell migration and invasion. Conversely, stable knockdown of FBI-1 remarkably reduced the motility of these cells with decreased expression of MT1-MMP. Promoter assay and chromatin immunoprecipitation study indicated that FBI-1 could directly interact with the promoter spanning ~600bp of the 5'-flanking sequence of MT1-MMP and enhanced its expression in a dose-dependent manner. Furthermore, stable knockdown and ectopic expression of FBI-1 decreased and increased cell proliferation respectively in OVCA 420, but not in the p53 null SKOV-3 cells.Conclusions: Our results suggested an important role of FBI-1 in ovarian cancer cell proliferation, cell mobility, and invasiveness, and that FBI-1 can be a potential target of chemotherapy. © 2010 Jiang et al; licensee BioMed Central Ltd.
ISSN	1476-4598 2011 Impact Factor: 3.993 2011 SCImago Journal Rankings: 0.504
DOI	http://dx.doi.org/10.1186/1476-4598-9-318
ISI Accession Number ID	WOS:000286383600001
PubMed Central ID	PMC3022670
References	References in Scopus

DC Field	Value
dc.contributor.author	Jiang, L
dc.contributor.author	Siu, MKY
dc.contributor.author	Wong, OGW
dc.contributor.author	Tam, KF
dc.contributor.author	Lam, EWF
dc.contributor.author	Ngan, HYS
dc.contributor.author	Le, XF
dc.contributor.author	Wong, ESY
dc.contributor.author	Chan, HY
dc.contributor.author	Cheung, ANY
dc.date.accessioned	2011-09-23T06:01:56Z
dc.date.available	2011-09-23T06:01:56Z
dc.date.issued	2010
dc.description.abstract	Background: FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) is a member of the POK (POZ and Kruppel) family of transcription factors and play important roles in cellular differentiation and oncogenesis. Recent evidence suggests that FBI-1 is expressed at high levels in a subset of human lymphomas and some epithelial solid tumors. However, the function of FBI-1 in human ovarian cancers remains elusive.Results: In this study, we investigated the role of FBI-1 in human ovarian cancers, in particularly, its function in cancer cell invasion via modulating membrane type 1-matrix metalloproteinase (MT1-MMP). Significantly higher FBI-1 protein and mRNA expression levels were demonstrated in ovarian cancers samples and cell lines compared with borderline tumors and benign cystadenomas. Increased FBI-1 mRNA expression was correlated significantly with gene amplification (P = 0.037). Moreover, higher FBI-1 expression was found in metastatic foci (P = 0.036) and malignant ascites (P = 0.021), and was significantly associated with advanced stage (P = 0.012), shorter overall survival (P = 0.032) and disease-free survival (P = 0.016). In vitro, overexpressed FBI-1 significantly enhanced cell migration and invasion both in OVCA 420 and SKOV-3 ovarian carcinoma cells, irrespective of p53 status, accompanied with elevated expression of MT1-MMP, but not MMP-2 or TIMP-2. Moreover, knockdown of MT1-MMP abolished FBI-1-mediated cell migration and invasion. Conversely, stable knockdown of FBI-1 remarkably reduced the motility of these cells with decreased expression of MT1-MMP. Promoter assay and chromatin immunoprecipitation study indicated that FBI-1 could directly interact with the promoter spanning ~600bp of the 5'-flanking sequence of MT1-MMP and enhanced its expression in a dose-dependent manner. Furthermore, stable knockdown and ectopic expression of FBI-1 decreased and increased cell proliferation respectively in OVCA 420, but not in the p53 null SKOV-3 cells.Conclusions: Our results suggested an important role of FBI-1 in ovarian cancer cell proliferation, cell mobility, and invasiveness, and that FBI-1 can be a potential target of chemotherapy. © 2010 Jiang et al; licensee BioMed Central Ltd.
dc.description.nature	published_or_final_version
dc.identifier.citation	Molecular Cancer, 2010, v. 9 [How to Cite?] DOI: http://dx.doi.org/10.1186/1476-4598-9-318
dc.identifier.doi	http://dx.doi.org/10.1186/1476-4598-9-318
dc.identifier.hkuros	192471
dc.identifier.isi	WOS:000286383600001
dc.identifier.issn	1476-4598 2011 Impact Factor: 3.993 2011 SCImago Journal Rankings: 0.504
dc.identifier.pmcid	PMC3022670
dc.identifier.pmid	21176152
dc.identifier.scopus	eid_2-s2.0-78650278812
dc.identifier.uri	http://hdl.handle.net/10722/139933
dc.identifier.volume	9
dc.language	eng
dc.publisher	BioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
dc.publisher.place	United Kingdom
dc.relation.ispartof	Molecular Cancer
dc.relation.references	References in Scopus
dc.rights	Creative Commons: Attribution 3.0 Hong Kong License
dc.rights	Molecular Cancer. Copyright © BioMed Central Ltd.
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	DNA-Binding Proteins - genetics - metabolism
dc.subject.mesh	Matrix Metalloproteinase 14 - genetics - metabolism
dc.subject.mesh	Ovarian Neoplasms - enzymology - pathology
dc.subject.mesh	Transcription Factors - genetics - metabolism
dc.title	Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers
dc.type	Article

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Author Affiliations

The University of Hong Kong
Imperial College London
University of Texas M. D. Anderson Cancer Center
Sichuan University