Estrogen defines the dynamics and destination of transactivated EGF receptor in breast cancer cells: role of S1P(3) receptor and Cdc42
Date
2013
Authors
Sukocheva, O.
Wadham, C.
Xia, P.
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Journal article
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Experimental Cell Research, 2013; 319(4):455-465
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Abstract
Sphingosine-1-phosphate (SIP) 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 SIP, 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.
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Copyright 2012 Elsevier