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10.1158/0008-5472.CAN-13-2733

http://scihub22266oqcxt.onion/10.1158/0008-5472.CAN-13-2733
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C4454481!4454481!24853546
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suck abstract from ncbi


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pmid24853546      Cancer+Res 2014 ; 74 (14): 3935-46
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  • NDY1/KDM2B functions as a master regulator of Polycomb complexes and controls self-renewal of breast cancer stem cells #MMPMID24853546
  • Kottakis F; Foltopoulou P; Sanidas I; Keller P; Wronski A; Dake BT; Ezell SA; Shen Z; Naber SP; Hinds PW; McNiel E; Kuperwasser C; Tsichlis PN
  • Cancer Res 2014[Jul]; 74 (14): 3935-46 PMID24853546show ga
  • The JmjC domain histone H3K36me2/me1 demethylase NDY1/KDM2B is overexpressed in various types of cancer. Here we show that knocking down NDY1 in a set of ten cell lines derived from a broad range of human tumors inhibited their anchorage-dependent and anchorage-independent growth by inducing senescence and/or apoptosis in some and by inhibiting G1 progression in all. We further show that the knockdown of NDY1 in mammary adenocarcinoma cell lines decreased the number, size and replating efficiency of mammospheres and downregulated the stem cell markers ALDH and CD44, while upregulating CD24. These findings combined, suggest that NDY1 is required for the self-renewal of cancer stem cells and are in agreement with additional findings showing that, tumor cells in which NDY1 was knocked down undergo differentiation and a higher number of them is required to induce mammary adenocarcinomas, upon orthotopic injection in animals. Mechanistically, NDY1 functions as a master regulator of a set of microRNAs that target several members of the polycomb complexes PRC1 and PRC2 and its knockdown results in the de-repression of these microRNAs and the downregulation of their polycomb targets. Consistent with these observations, NDY1/KDM2B is expressed at higher levels in basal-like triple negative breast cancers and its overexpression is associated with higher rates of relapse after treatment. In addition, NDY1-regulated microRNAs are downregulated in both normal and cancer mammary stem cells. Finally, in primary human breast cancer, NDY1/KDM2B expression correlates negatively with the expression of the NDY1-regulated microRNAs, and positively with the expression of their PRC targets.
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