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10.1093/neuonc/nou206.70 http://scihub22266oqcxt.onion/10.1093/neuonc/nou206.70 C4144540/?report=reader!4144540!C4144540     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Neuro+Oncol 2014 ; 16 (Suppl 3): iii19 Nephropedia Template TP {{tp|p=C4144540|t=2014. A NOVEL P53 BYSTANDER EFFECT INDUCES GLIOBLASTOMA CELL DEATH THROUGH A GLYCOSYLATION-DEPENDENT MECHANISM |pdf=|usr=}}{{C4144540}} gab.com Text A NOVEL P53 BYSTANDER EFFECT INDUCES GLIOBLASTOMA CELL DEATH THROUGH A GLYCOSYLATION-DEPENDENT MECHANISM JO: Neuro Oncol http://www.kidney.de/pget.php?&tw=1&pmid=C4144540 #FOAvip BACKGROUND: Mutations in the TP53 tumor suppressor gene are required for the development of many malignancies, including brain tumors. Yet, the molecular mechanisms underlying p53's anti-tumor effects remain incompletely understood. In the present study we demonstrate the existence of a novel cell-extrinsic mechanism whereby p53 can antagonize tumor growth. METHODS: To activate p53-dependent DNA damage, cells were either untreated (Ctrl) or treated with 25 µM etoposide (VP16), ultraviolet light (UV; 60 mJ per cm2) or ?-radiation (5 Gy). Gene and protein expression were analyzed by Northern Blot, Western blot and/or RT/PCR analyses. Standard apoptosis assays, crystal violet cytotoxicity assays, soft-agar colony formation assays and in vivo tumorigenicity experiments were used. RESULTS: We found that following DNA damage, cells with activated p53 can control the viability of adjacent tumor cells through secretion of galectin-3 (Gal-3), a ?-galactoside-binding lectin. Gal-3 specifically induced the killing of bystander cancer cells but not normal cells by paracrine induction of caspase 9-mediated apoptosis. Induction of Gal3 secretion in tumor cells could also antagonize glioblastoma tumor growth in subcutaneous and intracranial models. Mechanistically, p53 indirectly induced Gal-3 export through transcriptional regulation of p53-tumor suppressor activated pathway-6 (TSAP6), a key component of the non-classical exosome-mediated secretory pathway. Investigation into the mechanism of tumor-specific killing by Gal-3 revealed preferential binding to ?1 integrin on the surface of tumor cells due to differential post-translational N-glycosylation resulting from the coordinated upregulation of several glycosyltransferases in the tumor cells. CONCLUSIONS: The bystander apoptosis effect defined here is significant because it represents a novel paracrine tumor suppressive mechanism for p53, which increases our understanding of p53 function and has therapeutic implications. It is important for the optimization of chemo- and radiotherapies as well as reactivation of p53 through small molecule or gene therapies. These data also suggest that Gal-3 has potential as an anti-cancer therapeutic. This work was supported by NIH R01 CA163722. SECONDARY CATEGORY: n/a. Twit Text FOAVip A NOVEL P53 BYSTANDER EFFECT INDUCES GLIOBLASTOMA CELL DEATH THROUGH A GLYCOSYLATION-DEPENDENT MECHANISM ????Neuro Oncol http://www.kidney.de/pget.php?&tw=1&pmid=C4144540 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=C4144540 #FOAvip English Wikipedia <ref>{{Cite pmid|C4144540}}</ref> A NOVEL P53 BYSTANDER EFFECT INDUCES GLIOBLASTOMA CELL DEATH THROUGH A GLYCOSYLATION-DEPENDENT MECHANISM #MMPMIDC4144540 Van Meir EG; Lee SH; Khwaja FW; Zerrouqi A; Zhang Z; Olson JJ; Kaluzova M; Hadjipanayis CG; Devi NS Neuro Oncol 2014[Jul]; 16 (Suppl 3): iii19 PMIDC4144540show ga BACKGROUND: Mutations in the TP53 tumor suppressor gene are required for the development of many malignancies, including brain tumors. Yet, the molecular mechanisms underlying p53's anti-tumor effects remain incompletely understood. In the present study we demonstrate the existence of a novel cell-extrinsic mechanism whereby p53 can antagonize tumor growth. METHODS: To activate p53-dependent DNA damage, cells were either untreated (Ctrl) or treated with 25 µM etoposide (VP16), ultraviolet light (UV; 60 mJ per cm2) or ?-radiation (5 Gy). Gene and protein expression were analyzed by Northern Blot, Western blot and/or RT/PCR analyses. Standard apoptosis assays, crystal violet cytotoxicity assays, soft-agar colony formation assays and in vivo tumorigenicity experiments were used. RESULTS: We found that following DNA damage, cells with activated p53 can control the viability of adjacent tumor cells through secretion of galectin-3 (Gal-3), a ?-galactoside-binding lectin. Gal-3 specifically induced the killing of bystander cancer cells but not normal cells by paracrine induction of caspase 9-mediated apoptosis. Induction of Gal3 secretion in tumor cells could also antagonize glioblastoma tumor growth in subcutaneous and intracranial models. Mechanistically, p53 indirectly induced Gal-3 export through transcriptional regulation of p53-tumor suppressor activated pathway-6 (TSAP6), a key component of the non-classical exosome-mediated secretory pathway. Investigation into the mechanism of tumor-specific killing by Gal-3 revealed preferential binding to ?1 integrin on the surface of tumor cells due to differential post-translational N-glycosylation resulting from the coordinated upregulation of several glycosyltransferases in the tumor cells. CONCLUSIONS: The bystander apoptosis effect defined here is significant because it represents a novel paracrine tumor suppressive mechanism for p53, which increases our understanding of p53 function and has therapeutic implications. It is important for the optimization of chemo- and radiotherapies as well as reactivation of p53 through small molecule or gene therapies. These data also suggest that Gal-3 has potential as an anti-cancer therapeutic. This work was supported by NIH R01 CA163722. SECONDARY CATEGORY: n/a. äA NOVEL P53 BYSTANDER EFFECT INDUCES GLIOBLASTOMA CELL DEATH THROUGH A(epmc).pdf DeepDyve Pubget Overpricing