摘要
Tumor metastasis is considered as the main cause that contributes to high mortality during lung cancer progression. Autophagy is a self-cleaning process to maintain cell integrity of intracellular organelles and proteins. To date, the role of autophagy in lung tumor metastasis remains elusive. Here, we report that lung tumors display a heterogeneous expression pattern of the autophagy mediator LC3A, the high expression of which is associated with low metastasis risk. We found a group of lung cancer cells contain differential LC3A expression levels and exhibit plasticity characterized by distinct proliferative and invasive properties. Immunofluorescence staining and immunoblotting assays revealed that LC3A-mediated autophagy is more active in highly proliferative but minimally invasive lung cancer cells than their lowly proliferative but highly invasive counterpart. Clonogenic analysis and cell cycle assays showed that LC3A silencing attenuated cellular growth, causing G1/S cell cycle arrest in highly proliferative lung cancer cells. Highly proliferative lung cancer cells exhibited a higher oxygen consumption rate, accompanied with an elevated oxygen species (ROS) level, compared to their lowly proliferative counterpart. Pharmacological inhibition of autophagy with chloroquine promoted the ROS production in highly proliferative lung cancer cells but not in the highly invasive counterpart. SOX2 expression enhanced LC3A expression and promoted proliferation but inhibited invasiveness in lung cancer cells. Knockdown of LC3A expression in SOX2-high proliferative cells enriched SOX2-low cells, exhibiting decreased proliferation but increased invasiveness. Combined, our findings provide substantial evidence to suggest that LC3A cooperates with SOX2 signaling to regulate lung cancer cell plasticity. Citation Format: Chia-Cheng Miao, Wen Hwang, Yu-Ting Chou. Heterogeneous LC3A expression regulates lung cancer cell plasticity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4279.