Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 17 3 2025 06 02 411 419 Seyedeh Shadi Vaziri Department of Microbiology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran Elahe Tajbakhsh Department of Microbiology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran Faham Khamesipour Halal Research Center of the Islamic Republic of Iran, Iran Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran Hassan Momtaz Department of Microbiology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran 2025 03 13 2025 05 02 Background and Objectives: This study investigates the impact of Helicobacter pylori (H. pylori)-derived outer membrane vesicles (OMVs) on the regulation of Snail/β-Catenin cascade and the production of metastasis-related proteins, such as E-cadherin and Vimentin, in the 4T1 cell line. Materials and Methods: OMVs were purified from H. pylori (ATCC 700392) cultures and applied to 4T1 cells at concentrations of 1, 5, and 10 μg/mL, with untreated cells serving as controls. The MTT assay was employed to quantify cell viability. Expression profiles of +vimentin, Snail, α-SMA, and β-catenin genes were evaluated by qRT-PCR, while protein expression of E-cadherin and Vimentin was analyzed via immunohistochemistry. Data were analyzed using appropriate statistical methods with SPSS and GraphPad Prism software. Results: The MTT assay showed that 1 μg/mL OMVs were safe for normal cells. At this concentration, the expression of vimentin, Snail, α-SMA, and β-catenin genes significantly increased in the treatment group (P≤0.05). Additionally, Vimentin protein decreased, and E-cadherin protein increased (P≤0.05). Conclusion: H. pylori-derived OMVs activate the Snail/β-Catenin cascade, influencing inflammatory responses and metastasis-related proteins, ultimately reducing migration in advanced cancer stages by modulating Vimentin and E-cadherin expression. https://ijm.tums.ac.ir/index.php/ijm/article/view/5354 https://ijm.tums.ac.ir/index.php/ijm/article/download/5354/1783