Mammalian target of rapamycin (mTOR) is involved in the survival of cells mediated by chemokine receptor 7 through PI3K/Akt in metastatic squamous cell carcinoma of the head and neck
Mammalian target of rapamycin (mTOR) is involved in the survival of cells mediated by chemokine receptor 7 through PI3K/Akt in metastatic squamous cell carcinoma of the head and neck
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DOI：
10.1016/j.bjoms.2009.06.007
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发表时间：
2010-06-01
影响因子：
1.8
通讯作者：
Sun, Chang-Fu
中科院分区：
文献类型：
--
作者：
Liu, Fa-Yu;Zhao, Zhen-Jin;Sun, Chang-Fu
头颈部转移性鳞状细胞癌（SCC）表达趋化因子受体7（CCR 7）。其激活磷酸肌醇-3激酶（PI 3 K）以促进头颈部SCC细胞的侵袭和存活。我们推测哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，m-TOR）可能是CCR 7-PI 3 K通路的下游分子。结果表明，CCR 7与其配体CCL 19之间的相互作用诱导mTOR及其靶点p70 s6 k的磷酸化。这种磷酸化通过抑制CCR 7和PI 3 K/Akt而消除，表明mTOR参与CCR 7-PI 3 K级联反应。mTOR和CCR 7-PI 3 K的抑制剂还导致头颈部转移性SCC细胞的CCL 19诱导的死亡、凋亡和细胞周期停滞显著增加。总之，我们的数据表明mTOR在CCR 7诱导的SCC细胞存活中发挥了重要作用。(C)2009年英国口腔颌面外科医师协会。由爱思唯尔有限公司出版。保留所有权利。
Metastatic squamous cell carcinoma (SCC) of the head and neck expresses chemokine receptor 7 (CCR7). which activates phosphoinositide-3 kinase (PI3K) to promote invasion and survival of SCC cells in the head and neck. We hypothesised that mammalian target of rapamycin (m-TOR) may be the downstream molecule of the CCR7-PI3K pathway. Results have shown that interaction between CCR7 and its ligand CCL19 induces the phosphorylation of mTOR and its target p70s6k. This phosphorylation is abolished by inhibition of CCR7 and PI3K/Akt, indicating that mTOR is involved in the CCR7-PI3K cascade. The inhibitors of mTOR and CCR7-PI3K also lead to a significant increase in CCL19-induced death, apoptosis, and cell-cycle arrest of metastatic SCC cells in the head and neck. Taken together, our data indicate the important part played by mTOR in CCR7-induced survival of such SCC cells. (C) 2009 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.