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Oncogene, 2014-06, Vol.33 (26), p.3432-3440
2014
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Autor(en) / Beteiligte
Titel
COL11A1 promotes tumor progression and predicts poor clinical outcome in ovarian cancer
Ist Teil von
  • Oncogene, 2014-06, Vol.33 (26), p.3432-3440
Ort / Verlag
London: Nature Publishing Group UK
Erscheinungsjahr
2014
Quelle
EZB-FREE-00999 freely available EZB journals
Beschreibungen/Notizen
  • Biomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovarian cancer. Microarray analysis suggested that COL11A1 is a disease progression-associated gene that is linked to ovarian cancer recurrence and poor survival. Small interference RNA-mediated specific reduction in COL11A1 protein levels suppressed the invasive ability and oncogenic potential of ovarian cancer cells and decreased tumor formation and lung colonization in mouse xenografts. A combination of experimental approaches, including real-time RT–PCR, casein zymography and chromatin immunoprecipitation (ChIP) assays, showed that COL11A1 knockdown attenuated MMP3 expression and suppressed binding of Ets-1 to its putative MMP3 promoter-binding site, suggesting that the Ets-1–MMP3 axis is upregulated by COL11A1. Transforming growth factor (TGF)-beta (TGF-β1) treatment triggers the activation of smad2 signaling cascades, leading to activation of COL11A1 and MMP3. Pharmacological inhibition of MMP3 abrogated the TGF-β1-triggered, COL11A1-dependent cell invasiveness. Furthermore, the NF-YA-binding site on the COL11A1 promoter was identified as the major determinant of TGF-β1-dependent COL11A1 activation. Analysis of 88 ovarian cancer patients indicated that high COL11A1 mRNA levels are associated with advanced disease stage. The 5-year recurrence-free and overall survival rates were significantly lower ( P =0.006 and P =0.018, respectively) among patients with high expression levels of tissue COL11A1 mRNA compared with those with low expression. We conclude that COL11A1 may promote tumor aggressiveness via the TGF-β1–MMP3 axis and that COL11A1 expression can predict clinical outcome in ovarian cancer patients.
Sprache
Englisch
Identifikatoren
ISSN: 0950-9232
eISSN: 1476-5594
DOI: 10.1038/onc.2013.307
Titel-ID: cdi_proquest_miscellaneous_1555015416

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