Nuclear Signaling Pathways and Targeting Transcription in Cancer PDF
Preview Nuclear Signaling Pathways and Targeting Transcription in Cancer
Cancer Drug Discovery and Development Rakesh Kumar Editor Nuclear Signaling Pathways and Targeting Transcription in Cancer Cancer Drug Discovery and Development Series editor Beverly A. Teicher National Cancer Institute, Bethesda, MD, USA For further volumes: http://www.springer.com/series/7625 Rakesh Kumar Editor Nuclear Signaling Pathways and Targeting Transcription in Cancer Editor Rakesh Kumar Department of Biochemistry and Molecular Medicine School of Medicine and Health Sciences The George Washington University Washington , DC , USA ISBN 978-1-4614-8038-9 ISBN 978-1-4614-8039-6 (eBook) DOI 10.1007/978-1-4614-8039-6 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2013944683 © Springer Science+Business Media New York 2014 This work is subject to copyright. 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Printed on acid-free paper Humana Press is a brand of Springer Springer is part of Springer Science+Business Media (www.springer.com) Pref ace Regulatory nuclear pathways feeding into the transcription of cancer-relevant molecules have emerged as the next frontier in pathway-centered cancer therapeutics. The signifi cance of nuclear signaling in cancer is also evident by the convergence of a large number of signal transduction pathways continuously sensing extracellular milieu. The cumulative outcome of deregulated cytoplasmic and nuclear signaling is to provide a favorable environment for a cancer cell to survive by overriding death signals, to sustain an excessive hyper-mitogenic activity, to feed into deregulated cell cycle progression, and to support a defective segregation of genetic material during mitosis leading to genomic instability, to name a few essential hallmarks of cancer progression. Among other processes, chromatin remodeling and epigenetic modifi cations are two important nuclear regulatory arms of transcription that have offered a battery of exciting therapeutic opportunities in terms of specifi city by focusing on specifi c modifi cation or modifi cations of histone or nonhistone pro- teins, domain-targeting, enzymatic activities such as histone deacetylases, histone acetyltransferases, histone demethylases, or splicing factors – as all of these activi- ties are widely deregulated in multiple human cancers. A large body of work during the last decade has demonstrated that these are targetable areas of translational can- cer medicine, and therefore, a large number of small molecules or agents targeting these biological processes are rapidly moving through the preclinical development pipeline to clinical studies. Another compelling aspect of nuclear signaling in cancer therapeutics is its inherent role in controlling the transcription of cancer-promoting factors. As many of the target gene products of nuclear signaling have functional relevance in the cytoplasmic compartment, these molecules are also at the center of signaling cas- cades in the cytoplasm and infl uenced by extracellular environment. Interestingly, the barrier of cytoplasmic and nuclear signaling is broken by recent advances in the area of nuclear receptor tyrosine kinases, which were earlier thought to be limited to the cytoplasm. Another recent excitement in the fi eld stems from the translational control of the elements of metabolism, such as lipogenesis. In addition to therapeu- tic value, many of the pathways and molecules described above are also becoming v vi Preface prognostic biomarkers to monitor the progression of cancer or to assess the thera- peutic effi cacy of a given targeted therapy. Since nuclear signaling represents the funneling junction of upstream signaling and because it imparts selectivity at the level of transcription, the overall goal of this book is to enhance our understanding of relevant processes in an integrated manner in the context of cancer medicine. The editor felt it timely to compile this book, written by the leading authorities in the fi eld and contributing to an emerging therapeutic discipline of signaling control of transcription in cancer medicine. Washington, DC, USA Rakesh Kumar Contents Part I Gene Regulation and Cancer 1 Steroid Receptor Coactivators (SRCs) as Integrators of Multiple Signaling Pathways in Cancer Progression ....................... 3 Weiwen Long and Bert W. O’Malley 2 Role of Alteration/Defi ciency in Activation (ADA) Complex in Cell Cycle, Genomic Instability and Cancer .................................... 33 Shakur Mohibi, Shashank Srivastava, Hamid Band, and Vimla Band 3 RUNX2 Transcriptional Regulation in Development and Disease ................................................................... 57 Jessica L. Brusgard and Antonino Passaniti 4 Epigenetic Mechanisms of Cancer Metastasis ..................................... 87 Jing Liang and Yongfeng Shang Part II Signaling Pathway and Cancer 5 Regulatory Effects of Arsenic on Cellular Signaling Pathways: Biological Effects and Therapeutic Implications ................................. 107 Elspeth M. Beauchamp, Ruth Serrano, and Leonidas C. Platanias 6 Nuclear Factors Linking Cancer and Infl ammation ............................ 121 Kunzang Chosdol, Mohita Bhagat, Bhawana Dikshit, Evanka Madan, Parthaprasad Chattopadhyay, and Subrata Sinha 7 Regulation of the Jak/STATs Pathways by Histone Deacetylases ....... 155 David M. Woods, Maritza Lienlaf-Moreno, Eduardo Sotomayor, Edward Seto, and Alejandro Villagra vii viii Contents 8 Receptor Tyrosine Kinases in the Nucleus: Nuclear Functions and Therapeutic Implications in Cancers............................................. 189 Longfei Huo, Jennifer L. Hsu, and Mien-Chie Hung 9 Nucleolar Signaling Determines Cell Fate: The RP-Mdm2-p53 Axis Fine-Tunes Cellular Homeostasis ............... 231 Yong Liu and Yanping Zhang 10 Transcriptional Regulation of Lipogenesis as a Therapeutic Target for Cancer Treatment .................................... 259 Chenguang Wang, Jun-Yuan Ji, Lifeng Tian, and Richard G. Pestell Part III Protein Domains and Cancer Therapeutics 11 Selective Inhibition of Acetyl-Lysine Effector Domains of the Bromodomain Family in Oncology ............................................. 279 Susanne Müller, Hannah Lingard, and Stefan Knapp 12 Domain Specifi c Targeting of Cancer .................................................... 299 Pratik Chandrani and Amit Dutt Part IV Targeted Cancer Therapy 13 The Potential of Targeting Splicing for Cancer Therapy .................... 313 Ana Rita Grosso and Maria Carmo-Fonseca 14 Exploiting Cell Cycle Pathways in Cancer Therapy: New (and Old) Targets and Potential Strategies .................................. 337 Angela Alexander and Khandan Keyomarsi 15 Histone Demethylases in Prostate Cancer ............................................ 373 Ling-Yu Wang, Wenchang Guo, Kevin Kim, Mamata Pochampalli, Chiu-Lien Hung, Yoshihiro Izumiya, and Hsing-Jien Kung 16 Therapeutic Signifi cance of Chromatin Remodeling Complexes in Cancer .............................................................................. 399 Da-Qiang Li and Rakesh Kumar Index ................................................................................................................. 423 Contributors Angela Alexander Department of Experimental Radiation Oncology, Radiation Oncology , University of Texas, MD Anderson Cancer Center , Houston , TX , USA Hamid Band Departments of Genetics, Cell Biology and Anatomy; Biochemistry and Molecular Biology; Pathology and Microbiology; Pharmacology and Experimental Neuroscience, College of Medicine , Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center , Omaha , NE , USA Vimla Band Department of Genetics, Cell Biology and Anatomy ; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center , Omaha , NE , USA Elspeth M. Beauchamp Robert H. Lurie Comprehensive Cancer Center, Northwestern University , Chicago , IL , USA Mohita Bhagat Department of Biochemistry , All India Institute of Medical Sciences , New Delhi , Delhi , India Jessica L. Brusgard Department of Pathology , University of Maryland, Marlene & Stewart Greenebaum Cancer Center , Baltimore , MD , USA Maria Carmo-Fonseca Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , Lisbon , Portugal Pratik Chandrani Advanced Centre for Treatment, Research and Education in Cancer , Tata Memorial Centre , Kharghar , Navi Mumbai , India Parthaprasad Chattopadhyay Department of Biochemistry , All India Institute of Medical Sciences , New Delhi , Delhi , India Kunzang Chosdol Department of Biochemistry , All India Institute of Medical Sciences , New Delhi , Delhi , India ix
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