{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:52:07Z","timestamp":1775868727916,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the NIH, NIEHS, and DTT","award":["ZIA ES021196-27"],"award-info":[{"award-number":["ZIA ES021196-27"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High-risk human papillomavirus (HR-HPV; HPV-16) and cigarette smoking are associated with cervical cancer (CC); however, the underlying mechanism(s) remain unclear. Additionally, the carcinogenic components of tobacco have been found in the cervical mucus of women smokers. Here, we determined the effects of cigarette smoke condensate (CSC; 3R4F) on human ectocervical cells (HPV-16 Ect\/E6E7) exposed to CSC at various concentrations (10\u22126\u2013100 \u03bcg\/mL). We found CSC (10\u22123 or 10 \u03bcg\/mL)-induced proliferation, enhanced migration, and histologic and electron microscopic changes consistent with EMT in ectocervical cells with a significant reduction in E-cadherin and an increase in the vimentin expression compared to controls at 72 h. There was increased phosphorylation of receptor tyrosine kinases (RTKs), including Eph receptors, FGFR, PDGFRA\/B, and DDR2, with downstream Ras\/MAPK\/ERK1\/2 activation and upregulation of common EMT-related genes, TGFB\u00a0SNAI2, PDGFRB, and SMAD2. Our study demonstrated that CSC induces EMT in ectocervical cells with the upregulation of EMT-related genes, expression of protein biomarkers, and activation of RTKs that regulate TGFB expression, and other EMT-related genes. Understanding the molecular pathways and environmental factors that initiate EMT in ectocervical cells will help delineate molecular targets for intervention and define the role of EMT in the initiation and progression of cervical intraepithelial neoplasia and CC.<\/jats:p>","DOI":"10.3390\/ijms25094902","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T03:30:49Z","timestamp":1714534249000},"page":"4902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tobacco Smoke Condensate Induces Morphologic Changes in Human Papillomavirus-Positive Cervical Epithelial Cells Consistent with Epithelial to Mesenchymal Transition (EMT) with Activation of Receptor Tyrosine Kinases and Regulation of TGFB"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2783-1344","authenticated-orcid":false,"given":"Zaniya A.","family":"Mark","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Cancer Biology, Neuroscience, and Pharmacology, Meharry Medical College, Nashville, TN 37208, USA"},{"name":"Molecular Pathogenesis Group, Mechanistic Toxicology Branch, National Institute of Environmental Health Sciences, NIH, Research Trriangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Yu","sequence":"additional","affiliation":[{"name":"Molecular Pathogenesis Group, Mechanistic Toxicology Branch, National Institute of Environmental Health Sciences, NIH, Research Trriangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lysandra","family":"Castro","sequence":"additional","affiliation":[{"name":"Molecular Pathogenesis Group, Mechanistic Toxicology Branch, National Institute of Environmental Health Sciences, NIH, Research Trriangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohua","family":"Gao","sequence":"additional","affiliation":[{"name":"Molecular Pathogenesis Group, Mechanistic Toxicology Branch, National Institute of Environmental Health Sciences, NIH, Research Trriangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelle R.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Molecular Pathogenesis Group, Mechanistic Toxicology Branch, National Institute of Environmental Health Sciences, NIH, Research Trriangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deloris","family":"Sutton","sequence":"additional","affiliation":[{"name":"Comparative and Molecular Pathogenesis Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9100-0027","authenticated-orcid":false,"given":"Erica","family":"Scappini","sequence":"additional","affiliation":[{"name":"Signal Transduction Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4329-7910","authenticated-orcid":false,"given":"Charles J.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Signal Transduction Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"Wine","sequence":"additional","affiliation":[{"name":"Signal Transduction Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yitang","family":"Yan","sequence":"additional","affiliation":[{"name":"Molecular Pathogenesis Group, Mechanistic Toxicology Branch, National Institute of Environmental Health Sciences, NIH, Research Trriangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangeline","family":"Motley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, Physiology, Meharry Medical College, Nashville, TN 37208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7001-2985","authenticated-orcid":false,"given":"Darlene","family":"Dixon","sequence":"additional","affiliation":[{"name":"Molecular Pathogenesis Group, Mechanistic Toxicology Branch, National Institute of Environmental Health Sciences, NIH, Research Trriangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"ref_1","unstructured":"(2023, June 15). 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Today"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/4902\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:37:14Z","timestamp":1760107034000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/4902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25094902"],"URL":"https:\/\/doi.org\/10.3390\/ijms25094902","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,30]]}}}