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Activated Monocyte-derived TNF-α Upregulates HGF/c-Met to Trigger EMT of Hepatoma Cells

Published: 10 July 2020 Publication History

Abstract

Monocytes/macrophages are critical inflammatory components predominantly recruited to tumor tissue to facilitate tumor metastasis. However, the underlying regulatory mechanisms remain largely unclear. In the study, we show that tumor-secreted soluble factors are capable of activating monocytes to produce higher level of proinflammatory cytokine tumor necrosis factor alpha (TNF-α), which in turn functions on tumor cells to increase the expression hepatocyte growth factor (HGF) and c-Met in liver cancer cell line HepG2 cells. TNF-α is also able to induce epithelial-mesenchymal transition (EMT) in HepG2 cells, as displayed by the reduced E-Cadherin expression and increased amount of Vimentin, N-Cadherin, transcription factor SNAI1, and SNAI2, but not Twist. Furthermore, we demonstrated that TNF-α possesses the capability of promoting the migration of HepG2 cells, which can be partially impaired by blocking c-Met signaling pathway. Collectively, these data reveal that TNF-α derived from tumor activated monocytes is leading to the upregulation of HGF and c-Met, whose interaction is able to synergistically switch on the activation of HGF-c-Met signaling pathway to foster the EMT. Thus, enhanced secretion of TNF-α in monocytes may represent a novel mechanism linking the innate response to metastasis in human hepatocellular carcinoma, which provides novel strategy for anti-tumor therapy.

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  • (2023)Polyhydroxylated Fullerene C60(OH)40 Nanofilms Promote the Mesenchymal–Epithelial Transition of Human Liver Cancer Cells via the TGF-β1/Smad PathwayJournal of Inflammation Research10.2147/JIR.S415378Volume 16(3739-3761)Online publication date: Aug-2023

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  1. Activated Monocyte-derived TNF-α Upregulates HGF/c-Met to Trigger EMT of Hepatoma Cells

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    cover image ACM Other conferences
    ICBBT '20: Proceedings of the 2020 12th International Conference on Bioinformatics and Biomedical Technology
    May 2020
    163 pages
    ISBN:9781450375719
    DOI:10.1145/3405758
    Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

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    • NWPU: Northwestern Polytechnical University
    • Universidade Nova de Lisboa

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    Published: 10 July 2020

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    Author Tags

    1. Epithelial mesenchymal transition (EMT)
    2. Hepatocellular carcinoma
    3. Monocyte/macrophage
    4. TNF-α HGF-c-Met signaling pathway

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    • (2023)Polyhydroxylated Fullerene C60(OH)40 Nanofilms Promote the Mesenchymal–Epithelial Transition of Human Liver Cancer Cells via the TGF-β1/Smad PathwayJournal of Inflammation Research10.2147/JIR.S415378Volume 16(3739-3761)Online publication date: Aug-2023

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