title: The chromatin-modifying protein HMGA2 promotes atypical teratoid/rhabdoid cell tumorigenicity.
abstract: Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive pediatric central nervous system tumor. The poor prognosis of AT/RT warrants identification of novel therapeutic targets and strategies. High-mobility Group AT-hook 2 (HMGA2) is a developmentally important chromatin-modifying protein that positively regulates tumor growth, self-renewal, and invasion in other cancer types. High-mobility group A2 was recently identified as being upregulated in AT/RT tissue, but the role of HMGA2 in brain tumors remains unknown. We used lentiviral short-hairpin RNA to suppress HMGA2 in AT/RT cell lines and found that loss of HMGA2 led to decreased cell growth, proliferation, and colony formation and increased apoptosis. We also found that suppression of HMGA2 negatively affected in vivo orthotopic xenograft tumor growth, more than doubling median survival of mice from 58 days to 153 days. Our results indicate a role for HMGA2 in AT/RT in vitro and in vivo and demonstrate that HMGA2 is a potential therapeutic target in these lethal pediatric tumors.
authors.affiliation: From the Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center (HK, MH-C, MFW, CGE, EHR), Division of Pediatric Oncology (EHR), Johns Hopkins University School of Medicine, Bloomberg Children's Hospital, Baltimore, Maryland; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina (YK, BEW); and Division of Hematology, Oncology, and Blood and Bone Marrow Transplant, Children's Hospital Los Angeles (JX, AE-E); and the University of Southern California (AE-E), Los Angeles, California.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Kaur
authors.forename: Marianne
authors.initials: M
authors.lastname: Hütt-Cabezas
authors.forename: Melanie F
authors.initials: MF
authors.lastname: Weingart
authors.forename: Jingying
authors.initials: J
authors.lastname: Xu
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Kuwahara
authors.forename: Anat
authors.initials: A
authors.lastname: Erdreich-Epstein
authors.forename: Bernard E
authors.initials: BE
authors.lastname: Weissman
authors.forename: Charles G
authors.initials: CG
authors.lastname: Eberhart
authors.forename: Eric H
authors.initials: EH
authors.lastname: Raabe
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015197:Carcinogenicity Tests; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics* / Q000502:physiology; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018335:Rhabdoid Tumor / Q000473:pathology*; D013724:Teratoma / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D025743:HMGA2 Protein; D034741:RNA, Small Interfering