Liu Fa-Yu, Zhao Zhen-Jin, Li Peng, Ding Xue, Zong Zhi-Hong, Sun Chang-Fu
Oral and Maxillofacial Tumor Center, Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, No. 117, Nanjing Bei Jie, Heping District, Shenyang, Liaoning 110002, China.
Br J Oral Maxillofac Surg. 2010 Jun;48(4):291-6. doi: 10.1016/j.bjoms.2009.06.007. Epub 2009 Jul 16.
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 (mTOR) 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.
头颈部转移性鳞状细胞癌（SCC）表达趋化因子受体7（CCR7），其激活磷酸肌醇-3激酶（PI3K）以促进头颈部SCC细胞的侵袭和存活。我们推测雷帕霉素哺乳动物靶蛋白（mTOR）可能是CCR7-PI3K通路的下游分子。结果显示，CCR7与其配体CCL19之间的相互作用诱导了mTOR及其靶标p70s6k的磷酸化。抑制CCR7和PI3K/Akt可消除这种磷酸化，表明mTOR参与了CCR7-PI3K级联反应。mTOR和CCR7-PI3K的抑制剂还导致CCL19诱导的头颈部转移性SCC细胞死亡、凋亡和细胞周期停滞显著增加。综上所述，我们的数据表明mTOR在CCR7诱导的此类SCC细胞存活中发挥重要作用。
