title: Emerging Roles of Epigenetic Regulator Sin3 in Cancer.
abstract: Revolutionizing treatment strategies is an urgent clinical need in the fight against cancer. Recently the scientific community has recognized chromatin-associated proteins as promising therapeutic candidates. However, there is a need to develop more targeted epigenetic inhibitors with less toxicity. Sin3 family is one such target which consists of evolutionary conserved proteins with two paralogues Sin3A and Sin3B. Sin3A/B are global transcription regulators that provide a versatile platform for diverse chromatin-modifying activities. Sin3 proteins regulate key cellular functions that include cell cycle, proliferation, and differentiation, and have recently been implicated in cancer pathogenesis. In this chapter, we summarize the key concepts of Sin3 biology and elaborate the recent advancements in the role of Sin3 proteins in cancer with specific examples in multiple endocrine neoplasia type 2, pancreatic ductal adenocarcinoma, and triple negative breast cancer. Finally, a program to create an integrative approach for screening antitumor agents that target chromatin-associated factors like Sin3 is presented.
authors.affiliation: The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: N
authors.initials: N
authors.lastname: Bansal
authors.affiliation: New York University School of Medicine, New York, NY, United States.
authors.forename: G
authors.initials: G
authors.lastname: David
authors.affiliation: The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: E
authors.initials: E
authors.lastname: Farias
authors.affiliation: The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: samuel.waxman@mssm.edu.
authors.forename: S
authors.initials: S
authors.lastname: Waxman
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002843:Chromatin; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics / Q000473:pathology; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D012097:Repressor Proteins / Q000235:genetics*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms
chemical_list: D002843:Chromatin; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C492042:SIN3B protein, human; D056264:Sin3 Histone Deacetylase and Corepressor Complex
keywords: Cancer stem cells; Epigenetics; HDAC; Multiple endocrine neoplasia type 2; Pancreatic ductal adenocarcinoma; Sin3A; Sin3B; Triple negative breast cancer