HMGA2 sustains self-renewal and invasiveness of glioma-initiating cells.
Glioblastoma multiforme (GBM) is the most common type of brain tumors with dismal outcomes. The mesenchymal phenotype is the hallmark of tumor aggressiveness in GBMs. Perivascular smooth muscle cells (pericytes) are essential in homeostasis of normal and glioma tissues. Here we found HMGA2, an architectural transcription factor that promotes mesenchymal phenotypes in a number of solid tumors, is highly expressed in mesenchymal subtype of GBMs and labels both glioma pericytes and glioma-initiating cells (GICs). Accordingly, depletion of HMGA2 in GICs resulted in compromised self-renewal and tumorigenic capability, as well as undermined mesenchymal or pericyte differentiation. We further showed HMGA2 allows expressions of FOXM1 and PLAU to maintain GIC propagation, gliomagenesis and aggressiveness both in vitro and in vivo. Therefore, suppressing HMGA2-mediated GIC self-renewal and invasiveness might be a promising means to treat GBMs.
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences at Wuhan University, Wuhan 430072, China.
Xiaoling
X
Zhong
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences at Wuhan University, Wuhan 430072, China.
Xuan
X
Liu
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences at Wuhan University, Wuhan 430072, China.
Yamu
Y
Li
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences at Wuhan University, Wuhan 430072, China.
Man
M
Cheng
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences at Wuhan University, Wuhan 430072, China.
Wen
W
Wang
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences at Wuhan University, Wuhan 430072, China.
Kuan
K
Tian
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences at Wuhan University, Wuhan 430072, China.
Lili
L
Mu
Department of Neurosurgery, The Tenth Affiliated Hospital, Tongji University, Shanghai 200072, China.
Tao
T
Zeng
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences at Wuhan University, Wuhan 430072, China.
Ying
Y
Liu
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xiaobing
X
Jiang
College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Luyang
L
Yu
Department of Neurosurgery, The Tenth Affiliated Hospital, Tongji University, Shanghai 200072, China.
Liang
L
Gao
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences at Wuhan University, Wuhan 430072, China.
Yan
Y
Zhou
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014162:Transfection
D025743:HMGA2 Protein
cancer stem cell; cell invasion; glioma; pericyte; self-renewal