Modulation of cell death pathways in cancer stem cells: Targeting histone demethylases

作     者：Ravi Thakur Durga Prasad Mishra 

作者机构：Cell Death Research Laboratory Division of endocrinology Central Drug Research Institute Lucknow India 

出 版 物：《Advances in Bioscience and Biotechnology》 (生命科学与技术进展（英文）)

年 卷 期：2012年第3卷第6期

页      面：720-730页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Cancer Stem Cells Histone Lysine Demethylases Cell Death LSD1 KDM5A 

摘      要：Cancer stem cells (CSCs) are tumor initiating cells within the tumor mass;that play a critical role in cancer pathogenesis. CSCs regulate cancer cell survival, metastatic potential, resistance to conventional radio-chemotherapy, disease relapse and poor prognosis. Recent studies have established that the drug resistant cancers and cancer cell lines possess high stem cell like traits compared to their drug sensitive counterparts. Histone demethylases are recently been linked to drug induced reversible tolerant state in cancers. Lysine histone demethylases are enzymes those demethylate lysines in histones and can act as transcriptional repressors or activators. Apart from histones other cellular proteins like E2F1, Rb, STAT3 and p53 are also regulated by methylation and demethylation cycles. In cancer cells these enzymes regulate cell survival, migration, invasion, and proliferation. This review summarizes the current progress of research on the role of histone demethylases in supporting drug tolerant cancer stem cell state and their potential as a drug target.