a Department of Pulmonary and Critical Care Medicine, Huadong Hospital, Fudan University , Shanghai , China.
Cancer Biol Ther. 2019;20(4):537-545. doi: 10.1080/15384047.2018.1537999. Epub 2018 Nov 8.
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.
肺癌是世界上最常见的癌症之一，约占所有癌症死亡人数的 27%。然而，肺癌细胞发病机制的机制在很大程度上仍然难以捉摸。在这项研究中，我们研究了叉头框蛋白 P1（FOXP1）在肺癌发展中的作用。我们的 Oncomine 分析表明，FOXP1 在肺腺癌中与正常肺组织相比下调。FOXP1 的敲低通过调节趋化因子信号分子的基因，包括 CCR1、ADCY5、GNG7、VAV3 和 PLCB1，促进 PC9 和 A549 细胞的生长和侵袭。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，PC9 细胞中 FOXP1 的敲低通过 CCR1 信号通路在异种移植小鼠模型中促进肿瘤发生。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发挥重要作用。
