Increased perfluorooctanoic acid accumulation facilitates the migration and invasion of lung cancer cells via remodeling cell mechanics
Jie Mei, Jipeng Jiang, Li Zhao, Yue Pan, Ke Xu, Xinglong Gao, Jing Yuan, Xia Li, Yufei Wang, Liuxiang Wang, Ailin Zhao, Shasha Jiang, Xinlian Wang, Shaoqiong Yi, Shilin Li, Yueguang Xue, Yongfu Ma, Yang Liu, Yang Liu, Yawei Wang, Juan Li, Chunying Chen, Ying Liu, Ying Liu
Abstract
Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used in industrial and household products, raising serious concerns due to their environmental persistence and mobility. Epidemiological studies have reported potential carcinogenic risks of PFAS based on their widespread occurrence and population exposure. In this study, we observed that perfluorooctanoic acid (PFOA), a common PFAS, functions as a mechanical regulator in lung cancer cells. PFOA exposure reduces cell stiffness, thereby decreasing cell adhesion and enhancing immune evasion, ultimately exacerbating tumor metastasis. In various lung cancer models, more aggressive tumor metastases have been observed in the PFOA exposure group. Additionally, serum PFOA levels in patients with advanced lung adenocarcinoma were significantly higher than those in patients with early-stage disease. Mechanistically, the interaction between PFOA and transmembrane integrins in cancer cells triggers changes in cellular mechanical properties, leading to the reorganization of the cytoskeleton, and activation of the intracellular FAK-PI3K-Akt signaling pathway. Our findings demonstrate that in individuals with lung adenocarcinoma, PFOA can increase the risk of cancer metastasis even at daily exposure levels.