Epigenetics and Cancer Stem Cells: Unleashing, Hijacking, and Restricting Cellular Plasticity
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TLDR
Recent advances highlighting the interplay between epigenetics, genetics, and cell-to-cell signaling in cancer are reviewed, with particular emphasis on mechanisms relevant for cancer stem cell formation (CSC) and function.Abstract:
Epigenetic mechanisms have emerged as key players in cancer development which affect cellular states at multiple stages of the disease. During carcinogenesis, alterations in chromatin and DNA methylation resulting from genetic lesions unleash cellular plasticity and favor oncogenic cellular reprogramming. At later stages, during cancer growth and progression, additional epigenetic changes triggered by interaction with the microenvironment modulate cancer cell phenotypes and properties, and shape tumor architecture. We review here recent advances highlighting the interplay between epigenetics, genetics, and cell-to-cell signaling in cancer, with particular emphasis on mechanisms relevant for cancer stem cell formation (CSC) and function.read more
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The somatic genomic landscape of glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neil,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
TL;DR: In this article, the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs) was described, including several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA.
Journal ArticleDOI
Targeting cancer stem cell pathways for cancer therapy
Liqun Yang,Pengfei Shi,Gaichao Zhao,Jie Xu,Wen Peng,Jiayi Zhang,Guanghui Zhang,Xiaowen Wang,Zhen Dong,Fei Chen,Hongjuan Cui +10 more
TL;DR: Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials.
Journal ArticleDOI
Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment.
Anna Dirkse,Anna Golebiewska,Thomas Buder,Thomas Buder,Petr V. Nazarov,Arnaud Muller,Suresh Poovathingal,Nicolaas H. C. Brons,Sonia Leite,Nicolas Sauvageot,Dzjemma Sarkisjan,Mathieu Seyfrid,Sabrina Fritah,Daniel Stieber,Alesandro Michelucci,Frank Hertel,Christel Herold-Mende,Francisco Azuaje,Alexander Skupin,Rolf Bjerkvig,Andreas Deutsch,Anja Voss-Böhme,Anja Voss-Böhme,Simone P. Niclou +23 more
TL;DR: It is reported that cells expressing CSC-associated cell membrane markers in Glioblastoma do not represent a clonal entity defined by distinct functional properties and transcriptomic profiles, but rather a plastic state that most cancer cells can adopt.
Journal ArticleDOI
Cancer cell plasticity: Impact on tumor progression and therapy response.
Victoria da Silva-Diz,Laura Lorenzo-Sanz,Adrià Bernat-Peguera,Marta Lopez-Cerda,Purificación Muñoz +4 more
TL;DR: This work provides an overview of the dynamic transition for cancer cell states, the mechanisms governing cell plasticity and their impact on tumor progression, metastasis and therapy response and insights for establishing new therapeutic interventions.
Journal ArticleDOI
Stem cell programs in cancer initiation, progression, and therapy resistance
Tianzhi Huang,Xiao Song,Dandan Xu,Deanna Tiek,Anshika Goenka,Bingli Wu,Namratha Sastry,Bo Hu,Shi Yuan Cheng +8 more
TL;DR: This review highlights the key features and mechanisms that regulate CSC function in tumor initiation, progression, and therapy resistance, and discusses factors for CSC therapeutic resistance, such as quiescence, induction of epithelial-to-mesenchymal transition (EMT), and resistance to DNA damage-induced cell death.
References
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TL;DR: Mutations of NADP(+)-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas.
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TL;DR: It is found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients and the databases from this study are widely available to serve as a foundation for further investigations of AMl pathogenesis, classification, and risk stratification.
Journal ArticleDOI
The Somatic Genomic Landscape of Glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neill,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
TL;DR: Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM.
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.