{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T04:08:47Z","timestamp":1776485327275,"version":"3.51.2"},"reference-count":66,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T00:00:00Z","timestamp":1750464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-25-00080"],"award-info":[{"award-number":["24-25-00080"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Foodborne trematode infections are recognized as a significant risk factor for cholangiocarcinoma (CCA) in endemic regions. Infection with the liver fluke Opisthorchis felineus induces precursor lesions of CCA, including the biliary intraepithelial neoplasia. The mechanisms underlying liver-fluke-associated neoplasia remain poorly understood. This study aims to identify the role of EGFR and Toll-like receptor 4-associated signaling pathways in bile duct epithelial neoplasia linked to liver fluke infection in patients, animal models, and cell models. Elevated levels of EGFR and phosphorylated EGFR were observed in the bile duct epithelium of patients with cholangiocarcinoma, as well as in the bile duct epithelium of laboratory hamsters. The EGFR content correlated with the degree of bile duct epithelial neoplasia. Additionally, a significant increase in the cell proliferation and migration rates of human H69 cholangiocytes was found, whereas those of HepG2 hepatoma cells remained unaffected following the helminth excretory\u2013secretory product (ESP) treatment. An EGFR inhibitor eliminated the enhanced cell proliferation (p = 0.005) and migration (p = 0.001) rates. Similar outcomes were achieved using Marimastat, an inhibitor of TLR-4-associated metalloproteinases. Thus, our study unveils novel avenues for exploring the mechanisms of helminth-associated carcinogenesis and for identifying key components of ESPs that mediate their mitogenic effects.<\/jats:p>","DOI":"10.3390\/pathogens14070620","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T09:08:44Z","timestamp":1750669724000},"page":"620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The EGFR Signaling Pathway Is Involved in the Biliary Intraepithelial Neoplasia Associated with Liver Fluke Infection"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2951-5716","authenticated-orcid":false,"given":"Dmitry","family":"Ponomarev","sequence":"first","affiliation":[{"name":"Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), 10 Akad. Lavrentiev Ave., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oxana","family":"Zaparina","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), 10 Akad. Lavrentiev Ave., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9543-9005","authenticated-orcid":false,"given":"Anna","family":"Kovner","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), 10 Akad. Lavrentiev Ave., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Hadieva","sequence":"additional","affiliation":[{"name":"Clinical Hospital of the Khanty-Mansiysk Autonomus Okrug-Ugra, Khanty-Mansiysk 628013, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail","family":"Persidskij","sequence":"additional","affiliation":[{"name":"Clinical Hospital of the Khanty-Mansiysk Autonomus Okrug-Ugra, Khanty-Mansiysk 628013, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1054-2068","authenticated-orcid":false,"given":"Maria","family":"Pakharukova","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), 10 Akad. Lavrentiev Ave., Novosibirsk 630090, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, 2 Pirogova Str., Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.actatropica.2013.01.005","article-title":"Opisthorchis felineus, an emerging infection in Italy and its implication for the European Union","volume":"126","author":"Pozio","year":"2013","journal-title":"Acta Trop."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1017\/S0031182022000397","article-title":"Similarities and differences among the Opisthorchiidae liver flukes: Insights from Opisthorchis felineus","volume":"149","author":"Pakharukova","year":"2022","journal-title":"Parasitology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00159","DOI":"10.1016\/j.fawpar.2022.e00159","article-title":"Global changes in gene expression related to Opisthorchis felineus liver fluke infection reveal temporal heterogeneity of a mammalian host response","volume":"27","author":"Pakharukova","year":"2022","journal-title":"Food Waterborne Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"119494","DOI":"10.1016\/j.lfs.2021.119494","article-title":"A tumorigenic cell line derived from a hamster cholangiocarcinoma associated with Opisthorchis felineus liver fluke infection","volume":"277","author":"Mordvinov","year":"2021","journal-title":"Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lishai, E.A., Zaparina, O.G., Kapushchak, Y.K., Sripa, B., Hong, S.J., Cheng, G., and Pakharukova, M.Y. 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