HMGA2 sustains self-renewal and invasiveness of glioma-initiating cells
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Xiaoling Zhong1, Xuan Liu1, Yamu Li1, Man Cheng1, Wen Wang1, Kuan Tian1, Lili Mu1, Tao Zeng2, Ying Liu1, Xiaobing Jiang3, Luyang Yu4, Liang Gao2, Yan Zhou1
1Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences at Wuhan University, Wuhan 430072, China
2Department of Neurosurgery, The Tenth Affiliated Hospital, Tongji University, Shanghai 200072, China
3Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
4College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China
Liang Gao, email: email@example.com
Yan Zhou, email: firstname.lastname@example.org
Keywords: glioma, cancer stem cell, pericyte, self-renewal, cell invasion
Received: December 17, 2015 Accepted: May 20, 2016 Published: May 31, 2016
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.
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