PloS one, 2011-08, Vol.6 (8), p.e23790
2011
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- Autor(en) / Beteiligte
- Titel
- Aberrant activation of ERK/FOXM1 signaling cascade triggers the cell migration/invasion in ovarian cancer cells
- Ist Teil von
- PloS one, 2011-08, Vol.6 (8), p.e23790
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Forkhead box M1 (FOXM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FOXM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. Here, we characterized the role of ERK/FOXM1 signaling in mediating the metastatic potential of ovarian cancer cells. Immunohistochemical (IHC), immunoblotting and semi-quantitative RT-PCR analyses found that both phospho-ERK and FOXM1 were frequently upregulated in ovarian cancers. Intriguingly, the overexpressed phospho-ERK (p<0.001) and FOXM1 (p<0.001) were significantly correlated to high-grade ovarian tumors with aggressive behavior such as metastasized lymph node (5 out of 6). Moreover, the expressions of phospho-ERK and FOXM1 had significantly positive correlation (p<0.001). Functionally, ectopic expression of FOXM1B remarkably enhanced cell migration/invasion, while FOXM1C not only increased cell proliferation but also promoted cell migration/invasion. Conversely, inhibition of FOXM1 expression by either thiostrepton or U0126 could significantly impair FOXM1 mediated oncogenic capacities. However, the down-regulation of FOXM1 by either thiostrepton or U0126 required the presence of p53 in ovarian cancer cells. Collectively, our data suggest that over-expression of FOXM1 might stem from the constitutively active ERK which confers the metastatic capabilities to ovarian cancer cells. The impairment of metastatic potential of cancer cells by FOXM1 inhibitors underscores its therapeutic value in advanced ovarian tumors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0023790Titel-ID: cdi_plos_journals_1308335049
- Format
- –
- Schlagworte
- Analysis, Biology, Blotting, Western, Butadienes - pharmacology, Cancer, Cancer cells, Cancer metastasis, Cell adhesion & migration, Cell cycle, Cell growth, Cell Line, Cell Line, Tumor, Cell migration, Cell Movement, Cell proliferation, Cell Proliferation - drug effects, Development and progression, Dose-Response Relationship, Drug, Ectopic expression, Enzyme Inhibitors - pharmacology, Extracellular signal-regulated kinase, Extracellular Signal-Regulated MAP Kinases - genetics, Extracellular Signal-Regulated MAP Kinases - metabolism, Female, Forkhead Box Protein M1, Forkhead protein, Forkhead Transcription Factors - genetics, Forkhead Transcription Factors - metabolism, Gene Expression Regulation, Neoplastic - drug effects, Health aspects, Humans, Immunoblotting, Immunohistochemistry, Kinases, Lymph nodes, Matrix Metalloproteinase 9 - genetics, Matrix Metalloproteinase 9 - metabolism, Medicine, Metastases, Neoplasm Invasiveness, Nitriles - pharmacology, Ovarian cancer, Ovarian carcinoma, Ovarian Neoplasms - genetics, Ovarian Neoplasms - metabolism, Ovarian Neoplasms - pathology, Overexpression, p53 Protein, Phosphoproteins - genetics, Phosphoproteins - metabolism, Polymerase chain reaction, Protein Isoforms - genetics, Protein Isoforms - metabolism, Receptors, Urokinase Plasminogen Activator - genetics, Receptors, Urokinase Plasminogen Activator - metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Signaling, Thiostrepton, Thiostrepton - pharmacology, Tumor proteins, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Protein p53 - metabolism, Tumorigenesis, Tumors