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首页> 美国政府科技报告 >Signaling by ErbB Receptors in Breast Cancer: Regulation by Compartmentalization of Heterodimetric Receptor Complexes.
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Signaling by ErbB Receptors in Breast Cancer: Regulation by Compartmentalization of Heterodimetric Receptor Complexes.

机译：ErbB受体在乳腺癌中的信号传导：通过异位受体复合物的区室化调节。

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Herein we investigated the mechanisms of MLKK1 and Stat3 signaling pathways. MEKK1 is important in apoptosis of cancer cells following detachment of cells from their matrix and following genotoxin treatment. We determined the mode by which MEKK1 causes apoptosis, and the ability of specific anti-apoptotic pathways to circumvent MEKK1-induced apoptosis. Specifically, MEKK1-induced apoptosis requires cleavage by caspase 3 and activation of the TRAIL death receptor pathway. MEKK1-induced death is potentiated by inhibition of PI-3 kinase, and is blocked by Akt through inhibition of MEKK1 cleavage. We also examined the mode of Stat3 transport through the cytoplasm to the nucleus, which has remained elusive. Stat3 is an oncogene implicated in cancer cell survival. We report that the mechanism whereby Stat3 is transported through the cytoplasm involves receptor-mediated endocytosis. Disruption of endocytosis with specific inhibitors blocks Stat3 nuclear translocation and Stat3-dependent gene regulation. Inhibition of endocytosis also blocks IL-6 and v-Src induced Stat3 activation. Therefore, receptor-mediated endocytosis may be a general mechanism for transport of cytoplasmic signaling proteins to the nucleus.

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