Mei Jie, Jiang Jipeng, Li Zhao, Pan Yue, Xu Ke, Gao Xinglong, Yuan Jing, Li Lili, Wang Yufei, Wang Liuxiang, Zhao Ailin, Jiang Shasha, Wang Xinlian, Yi Shaoqiong, Li Shilin, Xue Yueguang, Ma Yongfu, Liu Yang, Wang Yawei, Li Juan, Chen Chunying, Liu Ying
New Cornerstone Science Laboratory, Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing 100190, China.
Proc Natl Acad Sci U S A. 2024 Dec 17;121(51):e2408575121. doi: 10.1073/pnas.2408575121. Epub 2024 Dec 12.
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.
全氟烷基和多氟烷基物质（PFAS）广泛应用于工业和家用产品中，由于其在环境中的持久性和流动性，引发了严重关注。流行病学研究报告称，基于PFAS的广泛存在和人群暴露情况，其具有潜在致癌风险。在本研究中，我们观察到常见的PFAS——全氟辛酸（PFOA）在肺癌细胞中起机械调节作用。PFOA暴露会降低细胞硬度，从而减少细胞黏附并增强免疫逃逸，最终加剧肿瘤转移。在各种肺癌模型中，PFOA暴露组观察到更具侵袭性的肿瘤转移。此外，晚期肺腺癌患者血清中的PFOA水平显著高于早期疾病患者。从机制上讲，PFOA与癌细胞中的跨膜整合素之间的相互作用会引发细胞力学性质的变化，导致细胞骨架重组，并激活细胞内FAK-PI3K-Akt信号通路。我们的研究结果表明，对于肺腺癌患者，即使是日常暴露水平的PFOA也会增加癌症转移风险。
