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The EGFR Signaling Pathway Is Involved in the Biliary Intraepithelial Neoplasia Associated with Liver Fluke Infection. / Ponomarev, Dmitry V.; Zaparina, Oxana; Kovner, Anna et al.

In: Pathogens, Vol. 14, No. 7, 2025, p. 620.

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Ponomarev DV, Zaparina O, Kovner A, Hadieva E, Persidskij M, Pakharukova M. The EGFR Signaling Pathway Is Involved in the Biliary Intraepithelial Neoplasia Associated with Liver Fluke Infection. Pathogens. 2025;14(7):620. doi: 10.3390/pathogens14070620

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Ponomarev, Dmitry V. ; Zaparina, Oxana ; Kovner, Anna et al. / The EGFR Signaling Pathway Is Involved in the Biliary Intraepithelial Neoplasia Associated with Liver Fluke Infection. In: Pathogens. 2025 ; Vol. 14, No. 7. pp. 620.

BibTeX

@article{2b7d3deb5c8649ee992ae97ec6ec4c5c,
title = "The EGFR Signaling Pathway Is Involved in the Biliary Intraepithelial Neoplasia Associated with Liver Fluke Infection",
abstract = "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–secretory 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.",
author = "Ponomarev, {Dmitry V.} and Oxana Zaparina and Anna Kovner and Elena Hadieva and Mikhail Persidskij and Maria Pakharukova",
note = "The research was funded by the Russian Science Foundation (Project No. 24-25-00080) (O.Z.).",
year = "2025",
doi = "10.3390/pathogens14070620",
language = "English",
volume = "14",
pages = "620",
journal = "Pathogens",
issn = "2076-0817",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "7",

}

RIS

TY - JOUR

T1 - The EGFR Signaling Pathway Is Involved in the Biliary Intraepithelial Neoplasia Associated with Liver Fluke Infection

AU - Ponomarev, Dmitry V.

AU - Zaparina, Oxana

AU - Kovner, Anna

AU - Hadieva, Elena

AU - Persidskij, Mikhail

AU - Pakharukova, Maria

N1 - The research was funded by the Russian Science Foundation (Project No. 24-25-00080) (O.Z.).

PY - 2025

Y1 - 2025

N2 - 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–secretory 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.

AB - 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–secretory 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.

UR - https://www.mendeley.com/catalogue/738c4855-bc56-32dc-a5cc-9872c6cf605a/

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105011499506&origin=inward

U2 - 10.3390/pathogens14070620

DO - 10.3390/pathogens14070620

M3 - Article

C2 - 40732668

VL - 14

SP - 620

JO - Pathogens

JF - Pathogens

SN - 2076-0817

IS - 7

ER -

ID: 68614525