Increased perfluorooctanoic acid accumulation facilitates the migration and invasion of lung cancer cells via remodeling cell mechanics
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.
Authors
- Liuxiang Wang
- Jipeng Jiang (ORCID: https://orcid.org/0000-0002-8954-7277)
- Shasha Jiang (ORCID: https://orcid.org/0009-0001-2400-9216)
- Jing Yuan (ORCID: https://orcid.org/0000-0002-3923-925X)
- Yue Pan (ORCID: https://orcid.org/0000-0001-7709-0508)
- Jie Mei (ORCID: https://orcid.org/0000-0001-9521-4287)
- Xinlian Wang
- Xinglong Gao (ORCID: https://orcid.org/0000-0003-3917-1950)
- Yueguang Xue (ORCID: https://orcid.org/0000-0002-5046-3682)
- Chunying Chen (ORCID: https://orcid.org/0000-0002-6027-0315)
- Ying Liu (ORCID: https://orcid.org/0000-0002-6540-0473)
- Juan Li (ORCID: https://orcid.org/0000-0002-0692-3370)
- Xia Li (ORCID: https://orcid.org/0000-0002-9794-2648)
- Yongfu Ma
- Yang Liu (ORCID: https://orcid.org/0000-0003-0820-0683)
- Shilin Li (ORCID: https://orcid.org/0000-0003-1195-2245)
- Ailin Zhao
- Yufei Wang (ORCID: https://orcid.org/0009-0002-5685-6580)
- Li Zhao (ORCID: https://orcid.org/0000-0003-2590-2417)
- Shaoqiong Yi
- Ke Xu (ORCID: https://orcid.org/0009-0007-6704-0479)
- Yawei Wang (ORCID: https://orcid.org/0009-0001-9151-6648)
Institutions
- Academy of Medical Sciences (GB)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Chinese General Hospital College of Nursing and Liberal Arts (PH)
- National Institutes for Food and Drug Control (CN)
- National Center for Nanoscience and Technology (CN)
- Research Center for Eco-Environmental Sciences (CN)
- Chinese People's Liberation Army (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2024-12-12
- DOI
- https://doi.org/10.1073/pnas.2408575121
- Citations
- 33
- Primary Topic
- Per- and polyfluoroalkyl substances research
- Type
- article
- Field-Weighted Citation Impact
- 8.26
Funders
- National Natural Science Foundation of China
- Major Research Plan