Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma
Krishna P.L. Bhat,Veerakumar Balasubramaniyan,Brian Vaillant,Ravesanker Ezhilarasan,Karlijn Hummelink,Faith Hollingsworth,Khalida Wani,Lindsey Heathcock,Johanna D. James,Lindsey D. Goodman,Siobhan Conroy,Lihong Long,Nina Lelic,Suzhen Wang,Joy Gumin,Divya Raj,Yoshinori Kodama,Aditya Raghunathan,Adriana Olar,Kaushal Joshi,Christopher E. Pelloski,Amy B. Heimberger,Se Hoon Kim,Daniel P. Cahill,Ganesh Rao,Wilfred F. A. den Dunnen,Hendrikus Boddeke,Heidi S. Phillips,Ichiro Nakano,Frederick F. Lang,Howard Colman,Erik P. Sulman,Kenneth Aldape +32 more
TLDR
It is shown that patient-derived glioma sphere cultures that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics, and it is suggested that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process.About:
This article is published in Cancer Cell.The article was published on 2013-09-09 and is currently open access. It has received 823 citations till now. The article focuses on the topics: Mesenchymal Glioblastoma & Tumor microenvironment.read more
Citations
More filters
Journal ArticleDOI
Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
Anoop P. Patel,Itay Tirosh,John J. Trombetta,Alex K. Shalek,Shawn M. Gillespie,Hiroaki Wakimoto,Daniel P. Cahill,Brian V. Nahed,William T. Curry,Robert L. Martuza,David N. Louis,Orit Rozenblatt-Rosen,Mario L. Suvà,Mario L. Suvà,Aviv Regev,Aviv Regev,Aviv Regev,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +19 more
TL;DR: The genome sequence of single cells isolated from brain glioblastomas was examined, which revealed shared chromosomal changes but also extensive transcription variation, including genes related to signaling, which represent potential therapeutic targets.
Journal ArticleDOI
Cancer stem cells in glioblastoma
Justin D. Lathia,Justin D. Lathia,Stephen C. Mack,Erin E. Mulkearns-Hubert,Claudia L.L. Valentim,Jeremy N. Rich,Jeremy N. Rich +6 more
TL;DR: To fulfill the future goal of developing novel therapies to collapse CSC dynamics, drawing parallels to other normal and pathological states that are highly interactive with their microenvironments and that use developmental signaling pathways will be beneficial.
Journal ArticleDOI
Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment.
Qianghu Wang,Baoli Hu,Xin Hu,Xin Hu,Hoon Kim,Massimo Squatrito,Lisa Scarpace,Ana C. deCarvalho,Sali Lyu,Pengping Li,Yan Li,Floris P. Barthel,Hee Jin Cho,Hee Jin Cho,Yu Hsi Lin,Nikunj Satani,Emmanuel Martinez-Ledesma,Siyuan Zheng,Edward I. Chang,Charles Etienne Gabriel Sauvé,Adriana Olar,Zheng D. Lan,Gaetano Finocchiaro,Joanna J. Phillips,Mitchel S. Berger,Konrad Gabrusiewicz,Guocan Wang,Eskil Eskilsson,Jian Hu,Tom Mikkelsen,Ronald A. DePinho,Florian L. Muller,Amy B. Heimberger,Erik P. Sulman,Do Hyun Nam,Do Hyun Nam,Roel G.W. Verhaak +36 more
TL;DR: Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence within weeks of diagnosis and at recurrence.
Journal ArticleDOI
m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program.
Sicong Zhang,Boxuan Simen Zhao,Aidong Zhou,Kangyu Lin,Shaoping Zheng,Zhike Lu,Zhike Lu,Yaohui Chen,Erik P. Sulman,Keping Xie,Oliver Bogler,Sadhan Majumder,Chuan He,Suyun Huang +13 more
TL;DR: This work uncovers a critical function for ALKBH5 and provides insight into critical roles of m6A methylation in glioblastoma and a long non-coding RNA antisense to FOXM1 (FOXM1-AS) promotes the interaction of AL KBH5 withFOXM1 nascent transcripts.
Journal ArticleDOI
NF-κB, an Active Player in Human Cancers
TL;DR: Because of its vital role in various biologic activities, components of the NF-κB pathway need to be carefully selected and evaluated to design targeted therapies.
References
More filters
Journal ArticleDOI
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Aravind Subramanian,Pablo Tamayo,Vamsi K. Mootha,Sayan Mukherjee,Benjamin L. Ebert,Michael A. Gillette,Amanda G. Paulovich,Scott L. Pomeroy,Todd R. Golub,Eric S. Lander,Jill P. Mesirov +10 more
TL;DR: The Gene Set Enrichment Analysis (GSEA) method as discussed by the authors focuses on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation.
Journal ArticleDOI
Bioconductor: open software development for computational biology and bioinformatics
Robert Gentleman,Vincent J. Carey,Douglas M. Bates,Benjamin M. Bolstad,Marcel Dettling,Sandrine Dudoit,Byron Ellis,Laurent Gautier,Yongchao Ge,Jeff Gentry,Kurt Hornik,Torsten Hothorn,Wolfgang Huber,Stefano Maria Iacus,Rafael A. Irizarry,Friedrich Leisch,Cheng Li,Martin Maechler,A. J. Rossini,Günther Sawitzki,Colin A. Smith,Gordon K. Smyth,Luke Tierney,Jean Yang,Jianhua Zhang +24 more
TL;DR: Details of the aims and methods of Bioconductor, the collaborative creation of extensible software for computational biology and bioinformatics, and current challenges are described.
Journal ArticleDOI
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Glynn Dennis,Brad T. Sherman,Douglas A. Hosack,Jun Jun Yang,Wei Gao,H. Clifford Lane,Richard A. Lempicki +6 more
TL;DR: DAMID is a web-accessible program that integrates functional genomic annotations with intuitive graphical summaries that assists in the interpretation of genome-scale datasets by facilitating the transition from data collection to biological meaning.
Journal ArticleDOI
MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma
Monika E. Hegi,Annie-Claire Diserens,Thierry Gorlia,Marie-France Hamou,Nicolas de Tribolet,Nicolas de Tribolet,Michael Weller,Johan M. Kros,Johannes A. Hainfellner,Warren P. Mason,Luigi Mariani,Jacoline E C Bromberg,Peter Hau,René O. Mirimanoff,J. Gregory Cairncross,Robert C. Janzer,Roger Stupp +16 more
TL;DR: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylation of theMGMT promoter did notHave such a benefit and were assigned to only radiotherapy.
Journal ArticleDOI
Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
Shideng Bao,Qiulian Wu,Roger E. McLendon,Yueling Hao,Qing Ming Shi,Anita B. Hjelmeland,Mark W. Dewhirst,Darell D. Bigner,Jeremy N. Rich +8 more
TL;DR: This work shows that cancer stem cells contribute to glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity, and suggests that CD133-positive tumour cells could be the source of tumour recurrence after radiation.
Related Papers (5)
Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1
Roel G.W. Verhaak,Katherine A. Hoadley,Elizabeth Purdom,Victoria Wang,Yuan-yuan Qi,Matthew D. Wilkerson,C. Ryan Miller,Li Ding,Todd R. Golub,Jill P. Mesirov,Gabriele Alexe,Michael S. Lawrence,Michael O'Kelly,Pablo Tamayo,Barbara A. Weir,Stacey Gabriel,Wendy Winckler,Supriya Gupta,Lakshmi Jakkula,Heidi S. Feiler,J. Graeme Hodgson,C. David James,Jann N. Sarkaria,Cameron Brennan,Ari B. Kahn,Paul T. Spellman,Richard K. Wilson,Terence P. Speed,Terence P. Speed,Joe W. Gray,Matthew Meyerson,Gad Getz,Charles M. Perou,Charles M. Perou,D. Neil Hayes +34 more
Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Roger Stupp,Warren P. Mason,Martin J. van den Bent,Michael Weller,Barbara Fisher,Martin J.B. Taphoorn,Karl Belanger,Alba A. Brandes,Christine Marosi,Ulrich Bogdahn,Jürgen Curschmann,Robert C. Janzer,Samuel K. Ludwin,Thierry Gorlia,Anouk Allgeier,Denis Lacombe,J. Gregory Cairncross,Elizabeth Eisenhauer,René O. Mirimanoff +18 more
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
Roger E. McLendon,Allan H. Friedman,Darrell D. Bigner,Erwin G. Van Meir,Daniel J. Brat,Gena M. Mastrogianakis,Jeffrey J. Olson,Tom Mikkelsen,Norman L. Lehman,Kenneth Aldape,W. K. Alfred Yung,Oliver Bogler,John N. Weinstein,Scott R. VandenBerg,Mitchel S. Berger,Michael D. Prados,Donna M. Muzny,Margaret Morgan,Steve Scherer,Aniko Sabo,Lynn Nazareth,Lora Lewis,Otis Hall,Yiming Zhu,Yanru Ren,Omar Alvi,Jiqiang Yao,Alicia Hawes,Shalini N. Jhangiani,Gerald R. Fowler,Anthony San Lucas,Christie Kovar,Andrew Cree,Huyen Dinh,Jireh Santibanez,Vandita Joshi,Manuel L. Gonzalez-Garay,Christopher A. Miller,Aleksandar Milosavljevic,Lawrence A. Donehower,David A. Wheeler,Richard A. Gibbs,Kristian Cibulskis,Carrie Sougnez,Timothy Fennell,Scott Mahan,Jane Wilkinson,Liuda Ziaugra,Robert C. Onofrio,Toby Bloom,Rob Nicol,Kristin G. Ardlie,Jennifer Baldwin,Stacey Gabriel,Eric S. Lander,Eric S. Lander,Li Ding,Robert S. Fulton,Michael D. McLellan,John W. Wallis,David E. Larson,Xiaoqi Shi,Rachel Abbott,Lucinda Fulton,Ken Chen,Daniel C. Koboldt,Michael C. Wendl,Rick Meyer,Yuzhu Tang,Ling Lin,John R. Osborne,Brian H. Dunford-Shore,Tracie L. Miner,Kim D. Delehaunty,Chris Markovic,Gary W. Swift,William Courtney,Craig Pohl,Scott Abbott,Amy Hawkins,Shin Leong,Carrie A. Haipek,Heather Schmidt,Maddy Wiechert,Tammi L. Vickery,Sacha Scott,David J. Dooling,Asif T. Chinwalla,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Gad Getz,Wendy Winckler,Roel G.W. Verhaak,Michael S. Lawrence,Michael J. T. O’Kelly,James A. Robinson,Gabriele Alexe,Rameen Beroukhim,Scott L. Carter,Derek Y. Chiang,Josh Gould,Supriya Gupta,Josh Korn,Craig H. Mermel,Jill P. Mesirov,Stefano Monti,Huy V. Nguyen,Melissa Parkin,Michael R. Reich,Nicolas Stransky,Barbara A. Weir,Levi A. Garraway,Todd R. Golub,Matthew Meyerson,Lynda Chin,Alexei Protopopov,Jianhua Zhang,Ilana Perna,Sandy Aronson,Narayanan Sathiamoorthy,Georgia Ren,Jun Yao,W. Ruprecht Wiedemeyer,Hyun Soo Kim,Won Kong Sek,Yonghong Xiao,Isaac S. Kohane,Jon G. Seidman,Peter J. Park,Raju Kucherlapati,Peter W. Laird,Leslie Cope,James G. Herman,Daniel J. Weisenberger,Fei Pan,David Van Den Berg,Leander Van Neste,Mi Yi Joo,Kornel E. Schuebel,Stephen B. Baylin,Devin Absher,Jun Li,Audrey Southwick,Shannon T. Brady,Amita Aggarwal,Tisha Chung,Gavin Sherlock,James D. Brooks,Richard M. Myers,Paul T. Spellman,Elizabeth Purdom,Lakshmi Jakkula,Anna Lapuk,Henry Marr,Shannon Dorton,Gi Choi Yoon,Ju Han,Amrita Ray,Victoria Wang,Steffen Durinck,Mark D. Robinson,Nicholas J. Wang,Karen Vranizan,Vivian Peng,Eric Van Name,Gerald V. Fontenay,John Ngai,John G. Conboy,Bahram Parvin,Heidi S. Feiler,Terence P. Speed,Terence P. Speed,Joe W. Gray,Cameron Brennan,Nicholas D. Socci,Adam B. Olshen,Barry S. Taylor,Barry S. Taylor,Alex E. Lash,Nikolaus Schultz,Boris Reva,Yevgeniy Antipin,Alexey Stukalov,Benjamin Gross,Ethan Cerami,Qing Wang Wei,Li-Xuan Qin,Venkatraman E. Seshan,Liliana Villafania,Magali Cavatore,Laetitia Borsu,Agnes Viale,William L. Gerald,Chris Sander,Marc Ladanyi,Charles M. Perou,D. Neil Hayes,Michael D. Topal,Katherine A. Hoadley,Yuan Qi,Sai Balu,Yan Shi,Junyuan Wu,Robert Penny,Michael L. Bittner,Troy Shelton,Elizabeth Lenkiewicz,Scott Morris,Debbie Beasley,Sheri Sanders,Ari B. Kahn,Robert Sfeir,Jessica Chen,David Nassau,Larry Feng,Erin Hickey,Anna D. Barker,Daniela S. Gerhard,Joseph G. Vockley,Carolyn C. Compton,Jim Vaught,Peter Fielding,Martin L. Ferguson,Carl F. Schaefer,Jinghui Zhang,Subhashree Madhavan,Kenneth H. Buetow,Francis S. Collins,Peter J. Good,Mark S. Guyer,Brad Ozenberger,Jane Peterson,Elizabeth J. Thomson +233 more