Nature communications · 2014
Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Leung Cecilia S, Yeung Tsz-Lun, Yip Kay-Pong, Pradeep Sunila, Balasubramanian Lavanya, Liu Jinsong, Wong Kwong-Kwok, Mangala Lingegowda S, Armaiz-Pena Guillermo N, Lopez-Berestein Gabriel, Sood Anil K, Birrer Michael J, Mok Samuel C
Аннотация
Ovarian cancer is the most lethal gynaecologic malignancy in the United States, and advanced serous ovarian adenocarcinoma is responsible for most ovarian cancer deaths. However, the stroma-derived molecular determinants that modulate patient survival are yet to be characterized. Here we identify a stromal gene signature for advanced high-grade serous ovarian cancer using microdissected stromal ovarian tumour samples and find that stromal microfibrillar-associated protein 5 (MFAP5) is a prognostic marker for poor survival. Further functional studies reveal that FAK/CREB/TNNC1 signalling pathways mediate the effect of MFAP5 on ovarian cancer cell motility and invasion potential. Targeting stromal MFAP5 using MFAP5-specific siRNA encapsulated in chitosan nanoparticles significantly decreases ovarian tumour growth and metastasis in vivo, suggesting that it may be a new modality of ovarian cancer treatment.
Предметные рубрики MeSH
ActinsAdenocarcinomaCalciumCell Line, TumorCell MovementContractile ProteinsCyclic AMP Response Element-Binding ProteinFemaleFocal Adhesion Protein-Tyrosine KinasesGene Expression Regulation, NeoplasticGene SilencingGlycoproteinsHumansImmunohistochemistryIntercellular Signaling Peptides and ProteinsNeoplasm MetastasisOvarian NeoplasmsPrognosisRNA, Small InterferingSignal TransductionStromal CellsTreatment OutcomeTroponin C