PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18 pathway
Abstract Particulate matter 2.5 (PM2.5) is a risk factor for lung cancer. In this study, we investigated the molecular mechanisms of PM2.5 exposure on lung cancer progression. We found that short‐term exposure to PM2.5 for 24 h activated the EGFR pathway in lung cancer cells (EGFR wild‐type and muta...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-06-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202217014 |
| _version_ | 1797280241686675456 |
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| author | Tong‐Hong Wang Kuo‐Yen Huang Chin‐Chuan Chen Ya‐Hsuan Chang Hsuan‐Yu Chen Chuen Hsueh Yi‐Tsen Liu Shuenn‐Chen Yang Pan‐Chyr Yang Chi‐Yuan Chen |
| author_facet | Tong‐Hong Wang Kuo‐Yen Huang Chin‐Chuan Chen Ya‐Hsuan Chang Hsuan‐Yu Chen Chuen Hsueh Yi‐Tsen Liu Shuenn‐Chen Yang Pan‐Chyr Yang Chi‐Yuan Chen |
| author_sort | Tong‐Hong Wang |
| collection | DOAJ |
| description | Abstract Particulate matter 2.5 (PM2.5) is a risk factor for lung cancer. In this study, we investigated the molecular mechanisms of PM2.5 exposure on lung cancer progression. We found that short‐term exposure to PM2.5 for 24 h activated the EGFR pathway in lung cancer cells (EGFR wild‐type and mutant), while long‐term exposure of lung cancer cells to PM2.5 for 90 days persistently promoted EGFR activation, cell proliferation, anchorage‐independent growth, and tumor growth in a xenograft mouse model in EGFR‐driven H1975 cancer cells. We showed that PM2.5 activated AhR to translocate into the nucleus and promoted EGFR activation. AhR further interacted with the promoter of TMPRSS2, thereby upregulating TMPRSS2 and IL18 expression to promote cancer progression. Depletion of TMPRSS2 in lung cancer cells suppressed anchorage‐independent growth and xenograft tumor growth in mice. The expression levels of TMPRSS2 were found to correlate with nuclear AhR expression and with cancer stage in lung cancer patient tissue. Long‐term exposure to PM2.5 could promote tumor progression in lung cancer through activation of EGFR and AhR to enhance the TMPRSS2‐IL18 pathway. |
| first_indexed | 2024-03-07T16:38:16Z |
| format | Article |
| id | doaj.art-5e9ebe0cfc3745a7aea86a1c3a1d3ea3 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T16:38:16Z |
| publishDate | 2023-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-5e9ebe0cfc3745a7aea86a1c3a1d3ea32024-03-03T09:19:32ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-06-01156n/an/a10.15252/emmm.202217014PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18 pathwayTong‐Hong Wang0Kuo‐Yen Huang1Chin‐Chuan Chen2Ya‐Hsuan Chang3Hsuan‐Yu Chen4Chuen Hsueh5Yi‐Tsen Liu6Shuenn‐Chen Yang7Pan‐Chyr Yang8Chi‐Yuan Chen9Tissue Bank, Chang Gung Memorial Hospital at Linkou Taoyuan TaiwanDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine National Taiwan University Taipei TaiwanTissue Bank, Chang Gung Memorial Hospital at Linkou Taoyuan TaiwanInstitute of Statistical Science Academia Sinica Taipei TaiwanInstitute of Statistical Science Academia Sinica Taipei TaiwanTissue Bank, Chang Gung Memorial Hospital at Linkou Taoyuan TaiwanGraduate Institute of Health Industry Technology and Research Center for Chinese Herbal Medicine, College of Human Ecology Chang Gung University of Science and Technology Taoyuan TaiwanInstitute of Biomedical Sciences Academia Sinica Taipei TaiwanInstitute of Biomedical Sciences Academia Sinica Taipei TaiwanTissue Bank, Chang Gung Memorial Hospital at Linkou Taoyuan TaiwanAbstract Particulate matter 2.5 (PM2.5) is a risk factor for lung cancer. In this study, we investigated the molecular mechanisms of PM2.5 exposure on lung cancer progression. We found that short‐term exposure to PM2.5 for 24 h activated the EGFR pathway in lung cancer cells (EGFR wild‐type and mutant), while long‐term exposure of lung cancer cells to PM2.5 for 90 days persistently promoted EGFR activation, cell proliferation, anchorage‐independent growth, and tumor growth in a xenograft mouse model in EGFR‐driven H1975 cancer cells. We showed that PM2.5 activated AhR to translocate into the nucleus and promoted EGFR activation. AhR further interacted with the promoter of TMPRSS2, thereby upregulating TMPRSS2 and IL18 expression to promote cancer progression. Depletion of TMPRSS2 in lung cancer cells suppressed anchorage‐independent growth and xenograft tumor growth in mice. The expression levels of TMPRSS2 were found to correlate with nuclear AhR expression and with cancer stage in lung cancer patient tissue. Long‐term exposure to PM2.5 could promote tumor progression in lung cancer through activation of EGFR and AhR to enhance the TMPRSS2‐IL18 pathway.https://doi.org/10.15252/emmm.202217014AhREGFRlung cancerPM2.5TMPRSS2 |
| spellingShingle | Tong‐Hong Wang Kuo‐Yen Huang Chin‐Chuan Chen Ya‐Hsuan Chang Hsuan‐Yu Chen Chuen Hsueh Yi‐Tsen Liu Shuenn‐Chen Yang Pan‐Chyr Yang Chi‐Yuan Chen PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18 pathway EMBO Molecular Medicine AhR EGFR lung cancer PM2.5 TMPRSS2 |
| title | PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18 pathway |
| title_full | PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18 pathway |
| title_fullStr | PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18 pathway |
| title_full_unstemmed | PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18 pathway |
| title_short | PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18 pathway |
| title_sort | pm2 5 promotes lung cancer progression through activation of the ahr tmprss2 il18 pathway |
| topic | AhR EGFR lung cancer PM2.5 TMPRSS2 |
| url | https://doi.org/10.15252/emmm.202217014 |
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