The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma.
The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma.
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DOI：
10.1126/scitranslmed.aac6762
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发表时间：
2015-09-09
影响因子：
17.1
通讯作者：
Rich JN
中科院分区：
文献类型：
--
作者：
Venere M;Horbinski C;Crish JF;Jin X;Vasanji A;Major J;Burrows AC;Chang C;Prokop J;Wu Q;Sims PA;Canoll P;Summers MK;Rosenfeld SS;Rich JN
恶性癌症的增殖和侵袭性导致了致命性。在胶质母细胞瘤中，这两个过程被认为是相互排斥的，因此被称为“要么生长要么生长”。在这里，我们确定了一个在这些不同的细胞过程之间穿梭的分子靶标——分子马达 KIF11。用高度特异性的小分子抑制剂抑制 KIF11，可以阻止对治疗更有抵抗力的胶质母细胞瘤肿瘤起始细胞（TIC 或癌症干细胞）以及非 TIC 的生长，并阻碍肿瘤的发生和 TIC 群体的自我更新。靶向 KIF11 还通过减少神经胶质瘤细胞侵袭来打击“继续或生长”细胞命运决定的另一臂。对患有原位胶质母细胞瘤的小鼠施用 KIF11 抑制剂可延长其生存期。 KIF11 作为肿瘤内异质性细胞生长和运动的共享分子调节剂，是胶质母细胞瘤的一个引人注目的靶点。
The proliferative and invasive nature of malignant cancers drives lethality. In glioblastoma, these two processes are presumed mutually exclusive and hence termed “go or grow”. Here, we identified a molecular target that shuttles between these disparate cellular processes—the molecular motor KIF11. Inhibition of KIF11 with a highly specific small molecule inhibitor stopped the growth of both the more treatment resistant glioblastoma tumor initiating cells (TICs, or cancer stem cells) as well as non-TICs and impeded tumor initiation and self-renewal of the TIC population. Targeting KIF11 also hit the other arm of the “go or grow” cell fate decision by reducing glioma cell invasion. Administration of a KIF11 inhibitor to mice bearing orthotopic glioblastoma prolonged their survival. In its role as a shared molecular regulator of cell growth and motility across intratumoral heterogeneity, KIF11 is a compelling target for glioblastoma.