Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis

被引:168
作者
Annibali, Daniela [1 ,2 ]
Whitfield, Jonathan R. [3 ,4 ]
Favuzzi, Emilia [2 ]
Jauset, Toni [3 ,4 ]
Serrano, Erika [3 ,4 ]
Cuartas, Isabel [3 ,4 ]
Redondo-Campos, Sara [3 ,4 ]
Folch, Gerard [3 ,4 ]
Gonzalez-Junca, Alba [3 ,4 ]
Sodir, Nicole M. [1 ,5 ]
Masso-Valles, Daniel [3 ,4 ]
Beaulieu, Marie-Eve [3 ,4 ]
Swigart, Lamorna B. [1 ]
Mc Gee, Margaret M. [6 ]
Somma, Maria Patrizia [2 ]
Nasi, Sergio [2 ]
Seoane, Joan [3 ,4 ,7 ]
Evan, Gerard I. [5 ]
Soucek, Laura [3 ,4 ]
机构
[1] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Pathol, San Francisco, CA 94143 USA
[2] Univ Roma La Sapienza, CNR, Ist Biol Med Mol & NanoBiotecnol, Dipartimento Biol & Biotecnol, I-00185 Rome, Italy
[3] Hosp Valle De Hebron, VHIO, Barcelona 08035, Spain
[4] Univ Autonoma Barcelona, E-08193 Barcelona, Spain
[5] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England
[6] Univ Coll Dublin, Sch Biomol & Biomed Sci, Conway Inst, Dublin 2, Ireland
[7] ICREA, Barcelona 08010, Spain
基金
欧洲研究理事会;
关键词
C-MYC; TYROSINE PHOSPHORYLATION; MALIGNANT ASTROCYTOMAS; SELF-RENEWAL; STEM-CELLS; CANCER; GLIOBLASTOMA; EXPRESSION; DRIVEN; GROWTH;
D O I
10.1038/ncomms5632
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.
引用
收藏
页数:11
相关论文
共 36 条
[1]
Amente S, 2012, AM J CANCER RES, V2, P330
[2]
TGF-β Receptor Inhibitors Target the CD44high/Id1high Glioma-Initiating Cell Population in Human Glioblastoma [J].
Anido, Judit ;
Saez-Borderias, Andrea ;
Gonzalez-Junca, Alba ;
Rodon, Laura ;
Folch, Gerard ;
Carmona, Maria A. ;
Prieto-Sanchez, Rosa M. ;
Barba, Ignasi ;
Martinez-Saez, Elena ;
Prudkin, Ludmila ;
Cuartas, Isabel ;
Raventos, Carolina ;
Martinez-Ricarte, Francisco ;
Antonia Poca, M. ;
Garcia-Dorado, David ;
Lahn, Michael M. ;
Yingling, Jonathan M. ;
Rodon, Jordi ;
Sahuquillo, Juan ;
Baselga, Jose ;
Seoane, Joan .
CANCER CELL, 2010, 18 (06) :655-668
[3]
Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses [J].
Assanah, Marcela ;
Lochhead, Richard ;
Ogden, Alfred ;
Bruce, Jeffrey ;
Goldman, James ;
Canoll, Peter .
JOURNAL OF NEUROSCIENCE, 2006, 26 (25) :6781-6790
[4]
Thermally Targeted Delivery of a c-Myc Inhibitory Polypeptide Inhibits Tumor Progression and Extends Survival in a Rat Glioma Model [J].
Bidwell, Gene L., III ;
Perkins, Eddie ;
Hughes, Joshua ;
Khan, Majid ;
James, Judy R. ;
Raucher, Drazen .
PLOS ONE, 2013, 8 (01)
[5]
U87MG Decoded: The Genomic Sequence of a Cytogenetically Aberrant Human Cancer Cell Line [J].
Clark, Michael James ;
Homer, Nils ;
O'Connor, Brian D. ;
Chen, Zugen ;
Eskin, Ascia ;
Lee, Hane ;
Merriman, Barry ;
Nelson, Stanley F. .
PLOS GENETICS, 2010, 6 (01)
[6]
MYC on the Path to Cancer [J].
Dang, Chi V. .
CELL, 2012, 149 (01) :22-35
[7]
Emerging roles of the SUMO pathway in mitosis [J].
Dasso, Mary .
CELL DIVISION, 2008, 3 (1)
[8]
Ding H, 2001, CANCER RES, V61, P3826
[9]
Feldkamp MM, 1999, INT J CANCER, V81, P118, DOI 10.1002/(SICI)1097-0215(19990331)81:1<118::AID-IJC20>3.3.CO
[10]
2-X