Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/snail signaling axis and expression of fascin

Bo Young Jeong, Kyung Hwa Cho, Kang Jin Jeong, Yun Yong Park, Jin Man Kim, Sun Young Rha, Chang Gyo Park, Gordon B. Mills, Jae Ho Cheong, Hoi Young Lee

    Research output: Contribution to journalArticlepeer-review

    12 Scopus citations

    Abstract

    The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We demonstrate that Rab25 increases β1 integrin levels and subsequent activation of EGFR and upregulation of VEGF-A expression, leading to increased Snail expression, epithelial-to-mesenchymal transition and cancer cell invasiveness. Strikingly, we identify that Snail mediates Rab25-induced cancer cell invasiveness through fascin expression and that ectopic expression of Rab25 aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a novel role of a β1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25-induced cancer cell aggressiveness through induction of fascin expression, thus providing novel biomarkers and potential therapeutic targets for Rab25-expressing cancer cells.

    Original languageEnglish (US)
    Article numbere435
    JournalExperimental and Molecular Medicine
    Volume50
    Issue number1
    DOIs
    StatePublished - 2018

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Clinical Biochemistry

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