15 research outputs found

    The biological role of the receptor-like protein tyrosine phosphatase LAR: a mouse model to study loss-of-function of LAR tyrosine phosphatase activity

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    Contains fulltext : mmubn000001_251882829.pdf (publisher's version ) (Open Access)Promotores : B. Wieringa en W. Hendriks166 p

    The biological role of the receptor-like protein tyrosine phosphatase LAR

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    The biological role of the receptor-like protein tyrosine phosphatase LAR

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    Item does not contain fulltextCell Biology, 7 oktober 1997Promotor : Wieringa, B. Co-promotor : Hendriks, W.J.A.J.166 p

    miRNA-520f Reverses Epithelial-to-Mesenchymal Transition by Targeting ADAM9 and TGFBR2

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    Contains fulltext : 174182.pdf (publisher's version ) (Closed access)Reversing epithelial-to-mesenchymal transition (EMT) in cancer cells has been widely considered as an approach to combat cancer progression and therapeutic resistance, but a limited number of broadly comprehensive investigations of miRNAs involved in this process have been conducted. In this study, we screened a library of 1120 miRNA for their ability to transcriptionally activate the E-cadherin gene CDH1 in a promoter reporter assay as a measure of EMT reversal. By this approach, we defined miR-520f as a novel EMT-reversing miRNA. miR-520f expression was sufficient to restore endogenous levels of E-cadherin in cancer cell lines exhibiting strong or intermediate mesenchymal phenotypes. In parallel, miR-520f inhibited invasive behavior in multiple cancer cell systems and reduced metastasis in an experimental mouse model of lung metastasis. Mechanistically, miR-520f inhibited tumor cell invasion by directly targeting ADAM9, the TGFbeta receptor TGFBR2 and the EMT inducers ZEB1, ZEB2, and the snail transcriptional repressor SNAI2, each crucial factors in mediating EMT. Collectively, our results show that miR-520f exerts anti-invasive and antimetastatic effects in vitro and in vivo, warranting further study in clinical settings. Cancer Res; 77(8); 2008-17. (c)2017 AACR

    NSC191928

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