The transcriptional modulator HMGA2 promotes stemness and tumorigenicity in glioblastoma.
Glioblastoma (GBM) contains a population of stem-like cells that promote tumor invasion and resistance to therapy. Identifying and targeting stem cell factors in GBM may lead to the development of more effective therapies. High Mobility Group AT-hook 2 (HMGA2) is a transcriptional modulator that mediates motility and self-renewal in normal and cancer stem cells. We identified increased expression of HMGA2 in the majority of primary human GBM tumors and cell lines compared to normal brain. Additionally, HMGA2 expression was increased in CD133+ GBM neurosphere cells compared to CD133- cells. Targeting HMGA2 with lentiviral short hairpin RNA (shRNA) led to decreased GBM stemness, invasion, and tumorigenicity. Ectopic expression of HMGA2 in GBM cell lines promoted stemness, invasion, and tumorigenicity. Our data suggests that targeting HMGA2 in GBM may be therapeutically beneficial.
Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA; Division of Pediatric Oncology, Johns Hopkins University, Bloomberg Children's Hospital, Room 11379, 1800 Orleans St, Baltimore, MD 21287, USA.
Harpreet
H
Kaur
Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Sabeen Zulfiqar
SZ
Ali
Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Lauren
L
Huey
Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA; Division of Pediatric Oncology, Johns Hopkins University, Bloomberg Children's Hospital, Room 11379, 1800 Orleans St, Baltimore, MD 21287, USA.
Marianne
M
Hütt-Cabezas
Division of Pediatric Oncology, Johns Hopkins University, Bloomberg Children's Hospital, Room 11379, 1800 Orleans St, Baltimore, MD 21287, USA.
Isabella
I
Taylor
Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Xing-Gang
XG
Mao
Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Melanie
M
Weingart
Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Qian
Q
Chu
Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Fausto J
FJ
Rodriguez
Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Charles G
CG
Eberhart
Division of Neuropathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA; Division of Pediatric Oncology, Johns Hopkins University, Bloomberg Children's Hospital, Room 11379, 1800 Orleans St, Baltimore, MD 21287, USA. Electronic address: eraabe2@jhmi.edu.
Eric H
EH
Raabe
D000071916:AC133 Antigen / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction; D018874:Spheroids, Cellular; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
D000071916:AC133 Antigen; D025743:HMGA2 Protein; C000606023:PROM1 protein, human
Clonogenicity; GSC; Glioma; HMGI-C; Motility