2. Academic Validation
  3. PM2.5 promotes lung cancer progression through activation of the AhR-TMPRSS2-IL18 pathway

PM2.5 promotes lung cancer progression through activation of the AhR-TMPRSS2-IL18 pathway

  • EMBO Mol Med. 2023 Mar 28;e17014. doi: 10.15252/emmm.202217014.
Tong-Hong Wang # 1 2 3 4,  Kuo-Yen Huang # 5,  Chin-Chuan Chen 1 4,  Ya-Hsuan Chang 6,  Hsuan-Yu Chen 6,  Chuen Hsueh 1 7,  Yi-Tsen Liu 2,  Shuenn-Chen Yang 8,  Pan-Chyr Yang 8 9 10,  Chi-Yuan Chen 1 2
Affiliations

Affiliations

  • 1 Tissue Bank, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
  • 2 Graduate Institute of Health Industry Technology and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
  • 3 Liver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
  • 4 Graduate Institute of Natural Products, Chang Gung University, Taoyuan, Taiwan.
  • 5 Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 6 Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
  • 7 Department of Anatomic Pathology, Chang Gung Memorial Hospital, Linko, Taoyuan, Taiwan.
  • 8 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • 9 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
  • 10 Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • # Contributed equally.
PMID: 36975376 DOI: 10.15252/emmm.202217014
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.

Keywords

AhR; EGFR; PM2.5; TMPRSS2; lung cancer.

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