2. Academic Validation
  3. Melatonin attenuates Helicobacter pylori-mediated cholangiocarcinoma-associated fibroblast activation via modulating integrin/FAK signaling pathway

Melatonin attenuates Helicobacter pylori-mediated cholangiocarcinoma-associated fibroblast activation via modulating integrin/FAK signaling pathway

  • Sci Rep. 2025 May 6;15(1):15780. doi: 10.1038/s41598-025-99980-z.
Sirinapha Klungsaeng 1 2,  Nuttanan Hongsrichan 1 2,  Apisit Chaidee 1 2,  Kitti Intuyod 3 2,  Porntip Pinlaor 4 2,  Sittiruk Roytrakul 5,  Kulthida Vaeteewoottacharn 6 2,  Sawanya Charoenlappanit 5,  Rungtiwa Dangtakot 7,  Narumon Mahaamnad 1 2,  Somchai Pinlaor 8 9
Affiliations

Affiliations

  • 1 Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
  • 2 Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand.
  • 3 Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
  • 4 Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
  • 5 Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
  • 6 Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
  • 7 Department of Medical Technology, Faculty of Allied Health Sciences, Nakhonratchasima College, Nakhon Ratchasima, 30000, Thailand.
  • 8 Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. psomec@kku.ac.th.
  • 9 Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand. psomec@kku.ac.th.
PMID: 40329017 DOI: 10.1038/s41598-025-99980-z
Abstract

The interaction of Helicobacter pylori with cancer-associated fibroblasts (CAFs) to promote cholangiocarcinoma (CCA) genesis is unclear. We aimed to demonstrate the effect and mechanism of H. pylori on function of CAFs in vitro as well as the role of melatonin as an anti-fibrotic agent capable of modulating CAFs. CAF cells were generated by co-culture of human fibroblasts (OUMS cell line) with O. viverrini-associated CCA cells (KKU-100 cell line). In the presence of H. pylori lysate, these CAF cells exhibited increased proliferation and migration. The interaction of CAFs and H. pylori lysate also promoted KKU-100 cell migration. Proteomic analysis revealed that the fibrosis-associated Integrin signaling pathway was enriched in CAFs stimulated by H. pylori lysate. Expression of focal adhesion kinase (FAK), a molecule that plays a pivotal role in cell proliferation and migration and known to be a downstream target of Integrin, was upregulated in CAFs exposed to H. pylori lysate. Interestingly, melatonin treatment significantly attenuated both proliferation and migration of CAFs by reducing FAK phosphorylation and its downstream PI3K and β-catenin. These results suggest that H. pylori promotes proliferation and migration of CAFs cells and possibly fibrosis via the Integrin/FAK signaling pathway, which could be attenuated by melatonin treatment.

Keywords

H. pylori cagA+; Bile duct cancer; Cancer-associated fibroblasts; FAK pathway; PI3K and β-catenin.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12289
    99.74%, FAK Inhibitor
    FAK