HMGA2 sustains self-renewal and invasiveness of glioma-initiating cells.
HMGA2 sustains self-renewal and invasiveness of glioma-initiating cells.
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HMGA2 维持神经胶质瘤起始细胞的自我更新和侵袭
DOI：
10.18632/oncotarget.9744
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发表时间：
2016-07-12
期刊：
影响因子：
--
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Zhong X;Liu X;Li Y;Cheng M;Wang W;Tian K;Mu L;Zeng T;Liu Y;Jiang X;Yu L;Gao L;Zhou Y
多形性胶质母细胞瘤（GBM）是最常见的脑肿瘤类型，结局令人沮丧。间充质表型是GBM中肿瘤侵袭性的标志。血管周围平滑肌细胞（周细胞）在正常和胶质瘤组织的稳态中是必不可少的。在这里，我们发现HMGA2，一种在许多实体瘤中促进间充质表型的结构转录因子，在GBM的间充质亚型中高度表达，并标记胶质瘤周细胞和胶质瘤起始细胞（GIC）。因此，GIC中HMGA2的消耗导致自我更新和致瘤能力受损，以及破坏间充质或周细胞分化。我们进一步表明，HMGA 2允许FOXM 1和PLAU的表达，以维持体外和体内GIC增殖，胶质瘤形成和侵袭性。因此，抑制HMGA2介导的GIC自我更新和侵袭性可能是治疗GBM的有希望的手段。
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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影响因子：
21.3
作者：
Laoukili, J;Kooistra, MRH;Medema, RH
通讯作者：
Medema, RH
影响因子：
16
作者：
Chiou, Guang-Yuh;Chien, Chian-Shiu;Chiou, Shih-Hwa
通讯作者：
Chiou, Shih-Hwa
影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.1221478110
发表时间：
2013-05-21
影响因子：
11.1
作者：
Mao, Ping;Joshi, Kaushal;Nakano, Ichiro
通讯作者：
Nakano, Ichiro