Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 activity and suppresses gliomas tumorigenicity.
Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 activity and suppresses gliomas tumorigenicity.
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DOI：
10.1038/srep07330
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发表时间：
2014-12-05
影响因子：
4.6
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Kim HS;Li A;Ahn S;Song H;Zhang W
胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤类型，含有干细胞样细胞（GSCs）亚群，是一种快速生长且通常致命的肿瘤。信号换能器和转录激活因子3 （STAT3）是维持GSCs的主要信号通路之一，但GSCs中STAT3失调的分子机制尚不清楚。在这里，我们证明了INPP5F，一种多磷酸肌肽磷酸酶，在胶质瘤患者的GSCs中有差异表达，并通过与STAT3相互作用和抑制其磷酸化被鉴定为STAT3信号的抑制剂。组成性表达的INPP5F抑制胶质母细胞瘤细胞的自我更新和增殖潜能，降低胶质母细胞瘤的致瘤性。此外，脑胶质瘤中INPP5F基因的缺失与较低的患者总体生存率显著相关。这些发现表明，INPP5F通过抑制STAT3通路在胶质瘤中是一种潜在的肿瘤抑制因子，而INPP5F的失调可能导致胶质瘤的形成。
Glioblastoma (GBM), the most common type of primary malignant brain tumors harboring a subpopulation of stem-like cells (GSCs), is a fast-growing and often fatal tumor. Signal Transducer and Activator of Transcription 3 (STAT3) is one of the major signaling pathways in GSCs maintenance but the molecular mechanisms underlying STAT3 deregulation in GSCs are poorly defined. Here, we demonstrate that Inositol Polyphosphate-5-Phosphatase F (INPP5F), one of the polyphosphoinositide phosphatases, is differentially expressed in GSCs from glioma patients, and is identified as an inhibitor of STAT3 signaling via interaction with STAT3 and inhibition of its phosphorylation. Constitutively expressed INPP5F showed to suppress self-renewal and proliferation potentials of glioblastoma cells and reduced tumorigenicity of glioblastoma. In addition, loss of INPP5F gene in gliomas is significantly correlated with lower overall patient survivals. These findings suggest that INPP5F is a potential tumor suppressor in gliomas via inhibition of STAT3 pathway, and that deregulation of INPP5F may lead to contribution to gliomagenesis.
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影响因子：
5.2
作者：
Madhavan, Subha;Zenklusen, Jean-Claude;Kotliarov, Yuri;Sahni, Himanso;Fine, Howard A.;Buetow, Kenneth
通讯作者：
Buetow, Kenneth
影响因子：
5.3
作者：
Bromberg, JF;Horvath, CM;Darnell, JE
通讯作者：
Darnell, JE
影响因子：
50.3
作者：
Kim E;Kim M;Woo DH;Shin Y;Shin J;Chang N;Oh YT;Kim H;Rheey J;Nakano I;Lee C;Joo KM;Rich JN;Nam DH;Lee J
通讯作者：
Lee J
影响因子：
56.9
作者：
Darnell, JE
通讯作者：
Darnell, JE
影响因子：
82.9
作者：
Trivedi, Chinmay M.;Luo, Yang;Epstein, Jonathan A.
通讯作者：
Epstein, Jonathan A.