Estrogen defines the dynamics and destination of transactivated EGF receptor in breast cancer cells: Role of S1P3 receptor and Cdc42

Olga Sukocheva, Carol Wadham, Pu Xia

    Research output: Contribution to journalArticlepeer-review

    21 Citations (Scopus)

    Abstract

    Sphingosine-1-phosphate (S1P) receptors mediate transactivation of epidermal growth factor receptor (EGFR) by estrogen (E2). Here we report that the amount of intracellular EGFR remains elevated after stimulation of MCF-7 cells with E2 and S1P, although membrane-localized EGFR and S1P3 receptors are quickly internalized. Co-localization of internalized EGFR and LAMP-2 was lower in cells treated with E2/S1P, suggesting that endosomal EGFR might be directed for recycling instead of degradation. In addition, we found that E2/S1P activated Cdc42 and that knockdown of Cdc42 restores fast EGFR degradation after E2/S1P stimulation. Inhibition of S1P3 receptors prevented E2-induced activation of Cdc42, supporting the important role of the S1P receptor in E2 signaling. This is a novel mechanism further defining the effect of E2/S1P on the EGFR transactivation in breast cancer cells.

    Original languageEnglish
    Pages (from-to)455-465
    Number of pages11
    JournalExperimental Cell Research
    Volume319
    Issue number4
    DOIs
    Publication statusPublished - 15 Feb 2013

    Keywords

    • Breast cancer
    • Cdc42
    • EGFR
    • Estrogen
    • Sphingosine-1-phosphate

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