Downregulation of cell surface CA125/MUC16 induces epithelial-to-mesenchymal transition and restores EGFR signalling in NIH:OVCAR3 ovarian carcinoma cells.


BACKGROUND:Epithelial ovarian cancer (EOC) cells are prone to metastasise throughout the peritoneal cavity. The epithelial-to-mesenchymal transition (EMT) is a necessary step towards metastatic tumour progression. CA125/MUC16 mucin is a high-molecular-weight glycoprotein overexpressed in the majority of serous carcinomas, suggesting a possible role in the pathogenesis of these cancers. METHODS:The role of CA125/MUC16 in EMT was investigated using single-chain antibody-mediated knockdown of cell surface CA125/MUC16 in overexpressing EOC NIH:OVCAR3 cells. RESULTS:CA125/MUC16 knockdown was associated with morphological alterations along with decreased surface expression of epithelial markers (E-cadherin, cytokeratin-18) and increased expression of mesenchymal markers (N-cadherin, vimentin). Co-immunoprecipitation experiments revealed that CA125/MUC16 binds to E-cadherin and β-catenin complexes. The in vitro studies showed disruption of cell-cell junctions, enhanced motility, migration and invasiveness in CA125/MUC16 knockdown cells. Enhanced epidermal growth factor receptor (EGFR) activation was observed in CA125/MUC16 knockdown cells along with increased Akt and ERK1/2 phosphorylation, which are downstream effectors of EGFR, and increased MMP-2 and MMP-9 expression and activities. Epidermal growth factor receptor inhibition strongly inhibited the motility of CA125/MUC16 knockdown cells. CONCLUSIONS:Our findings suggest that CA125/MUC16 plays a role in EMT, presumably through its interaction with E-cadherin and β-catenin complexes and by modulating EGFR and its downstream signalling pathway in NIH:OVCAR3 cells.


Br J Cancer


Comamala M,Pinard M,Thériault C,Matte I,Albert A,Boivin M,Beaudin J,Piché A,Rancourt C




Has Abstract


2011-03-15 00:00:00














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    abstract:BACKGROUND:Eukaryotic translation elongation factor 1A2 (eEF1A2) is a known proto-oncogene. We proposed that stimulation of the eEF1A2 expression in cancer tissues is caused by the loss of miRNA-mediated control. METHODS:Impact of miRNAs on eEF1A2 at the mRNA and protein levels was examined by qPCR and western blot, r...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Vislovukh A,Kratassiouk G,Porto E,Gralievska N,Beldiman C,Pinna G,El'skaya A,Harel-Bellan A,Negrutskii B,Groisman I

    更新日期:2013-06-11 00:00:00

  • Effect of prostaglandins and hormones on cyclic AMP formation in rat hepatomas and liver tissue.

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    pub_type: 杂志文章


    authors: Brønstad GO,Christoffersen T,Johansen EJ,Oye I

    更新日期:1978-12-01 00:00:00

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    abstract::In addition to hypoxia, acidic extracellular pH (pH(e)) is recognised as one of the microenvironmental characteristics of solid tumours. A number of studies have examined ways to increase tumour acidity in order to improve tumour-specific targeting of certain drugs and the effectiveness of hyperthermia. However, previ...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Kalliomäki T,Hill RP

    更新日期:2004-05-04 00:00:00

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    authors: Hsieh LL,Huang TH,Chen IH,Liao CT,Wang HM,Lai CH,Liou SH,Chang JT,Cheng AJ

    更新日期:2005-01-17 00:00:00

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    authors: Wang ZX,Wang HY,Wu MC

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    authors: Ohradanova A,Gradin K,Barathova M,Zatovicova M,Holotnakova T,Kopacek J,Parkkila S,Poellinger L,Pastorekova S,Pastorek J

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    更新日期:2004-08-16 00:00:00

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    pub_type: 杂志文章


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    更新日期:1977-07-01 00:00:00

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    authors: Bader S,Walker M,Harrison D

    更新日期:2000-12-01 00:00:00

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    authors: Ito Y,Takeda T,Sakon M,Tsujimoto M,Higashiyama S,Noda K,Miyoshi E,Monden M,Matsuura N

    更新日期:2001-05-18 00:00:00

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    更新日期:1988-08-01 00:00:00

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    pub_type: 杂志文章,多中心研究


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    abstract::This article was originally published under a standard license to Publish, but has now been made available under a CC BY license. The PDF and HTML versions of the paper have been modified accordingly.An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

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    pub_type: 已发布勘误


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    pub_type: 杂志文章


    authors: Tokunaga T,Nakamura M,Oshika Y,Abe Y,Ozeki Y,Fukushima Y,Hatanaka H,Sadahiro S,Kijima H,Tsuchida T,Yamazaki H,Tamaoki N,Ueyama Y

    更新日期:1999-01-01 00:00:00

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    authors: Ekert H,Waters KD,Smith PJ,Matthews RN,Ellis WM

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    pub_type: 杂志文章


    authors: Kölby L,Bernhardt P,Johanson V,Schmitt A,Ahlman H,Forssell-Aronsson E,Mäcke H,Nilsson O

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    authors: Kommoss S,du Bois A,Ridder R,Trunk MJ,Schmidt D,Pfisterer J,Kommoss F,AGO-OVAR.

    更新日期:2007-01-29 00:00:00

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    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Gustafsson L,Adami HO

    更新日期:1989-07-01 00:00:00

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    abstract::Recent studies involving animal models of cancer and clinicopathological analyses of human tumours suggest that the growth of lymphatic vessels (lymphangiogenesis) in or nearby tumours is associated with the metastatic spread of cancer. The best validated molecular signalling system for tumour lymphangiogenesis involv...

    journal_title:British journal of cancer

    pub_type: 杂志文章,评审


    authors: Achen MG,Mann GB,Stacker SA

    更新日期:2006-05-22 00:00:00

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    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Gyllensten U,Sanner K,Gustavsson I,Lindell M,Wikström I,Wilander E

    更新日期:2011-08-23 00:00:00

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    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: De Cesare M,Pratesi G,Giusti A,Polizzi D,Zunino F

    更新日期:1998-01-01 00:00:00

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    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Hilmy M,Campbell R,Bartlett JM,McNicol AM,Underwood MA,McMillan DC

    更新日期:2006-11-06 00:00:00

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    journal_title:British journal of cancer

    pub_type: 杂志文章,随机对照试验


    authors: Spencer SK,Pommier AJ,Morgan SR,Barry ST,Robertson JD,Hoff PM,Jürgensmeier JM

    更新日期:2013-11-26 00:00:00