Knockdown of FOXP1 promotes the development of lung adenocarcinoma
Knockdown of FOXP1 promotes the development of lung adenocarcinoma
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DOI：
10.1080/15384047.2018.1537999
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发表时间：
2019-04-03
影响因子：
3.6
通讯作者：
Xu, Yi
中科院分区：
文献类型：
--
作者：
Sheng, Hua;Li, Xiangyang;Xu, Yi
肺癌是世界上最常见的癌症之一，约占所有癌症死亡的27%。然而，肺癌细胞的发病机制在很大程度上仍然难以捉摸。在这项研究中，我们研究了叉头盒蛋白P1（FOXP1）在肺癌发展中的作用。我们的Oncomine分析显示，与正常肺组织相比，FOXP1在肺腺癌中下调。FOXP1的敲低通过调节趋化因子信号分子的基因促进PC9和A549细胞的生长和侵袭，所述趋化因子信号分子包括CCR 1、ADCY 5、GNG 7、VAV 3和PLCB 1。CCR1和FOXP1的同时敲低减弱了FOXP1敲低诱导的肺癌细胞生长增加。最后，在异种移植小鼠模型中，PC9细胞中FOXP1的敲低通过CCR1信号传导促进肿瘤发生。总之，我们的数据表明FOXP1通过抑制趋化因子信号通路在预防肺腺癌发展中起重要作用。
Lung cancer is one of the most common cancers in the world, which accounts for about 27% of all cancer deaths. However, the mechanisms underlying the pathogenesis of lung cancer cells remain largely elusive. In this study, we examined the role of the Forkhead box protein P1 (FOXP1) in lung cancer development. Our Oncomine analysis shows that FOXP1 is downregulated in lung adenocarcinoma compared with normal lung tissue. Knockdown of FOXP1 promotes the growth and invasion of PC9 and A549 cells by regulating genes of chemokine signaling molecules, including CCR1, ADCY5, GNG7, VAV3, and PLCB1. Simultaneous knockdown of CCR1 and FOXP1 attenuated FOXP1 knockdown-induced increase of lung cancer cell growth. Finally, knockdown of FOXP1 in PC9 cells promotes the tumorigenesis via CCR1 signaling in xenograft mouse model. Taken together, our data suggest that FOXP1 plays important roles in preventing lung adenocarcinoma development via suppressing chemokine signaling pathways.