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Syntaxin 6-mediated Golgi translocation plays an important role in nuclear functions of EGFR through microtubule-dependent trafficking

Oncogene volume 33, pages 756–770 (2014)Cite this article

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Abstract

Receptor tyrosine kinases (RTKs) are cell surface receptors that initiate signal cascades in response to ligand stimulation. Abnormal expression and dysregulated intracellular trafficking of RTKs have been shown to be involved in tumorigenesis. Recent evidence shows that these cell surface receptors translocate from cell surface to different cellular compartments, including the Golgi, mitochondria, endoplasmic reticulum (ER) and the nucleus, to regulate physiological and pathological functions. Although some trafficking mechanisms have been resolved, the mechanism of intracellular trafficking from cell surface to the Golgi is not yet completely understood. Here we report a mechanism of Golgi translocation of epidermal growth factor receptor (EGFR) in which EGF-induced EGFR travels to the Golgi via microtubule-dependent movement by interacting with dynein and fuses with the Golgi through syntaxin 6-mediated membrane fusion. We also demonstrate that the microtubule- and syntaxin 6-mediated Golgi translocation of EGFR is necessary for its consequent nuclear translocation and nuclear functions. Thus, together with previous studies, the microtubule- and syntaxin 6-mediated trafficking pathway from cell surface to the Golgi, ER and the nucleus defines a comprehensive trafficking route for EGFR to travel from cell surface to the Golgi and the nucleus.

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Acknowledgements

We thank Dr B Storrie (University of Arkansas for Medical Sciences) for providing the GalNac T2-GFP plasmid. This study was partially supported by the following grants: National Institutes of Health Grants CA109311 and CA099031 (to MC Hung); Cancer Research Center of Excellence (D0H101-TD-C-111-005, Taiwan); Private University Grant (NSC99-2632-B-039-001-MY3, Taiwan); Program for Stem Cell and Regenerative Medicine Frontier Research (NSC100-2321-B-039-002, Taiwan); International Research-Intensive Centers of Excellence in Taiwan (NSC101-2911-I-002-303, Taiwan); The University of Texas MD Anderson–China Medical University and Hospital Sister Institution Fund; National Institutes of Health through MD Anderson’s Cancer Center Support Grant and the Center for Biological Pathways (CA016672); Patel Memorial Breast Cancer Research Fund.

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Authors and Affiliations

  1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Y Du, J Shen, J L Hsu, Z Han, M-C Hsu, C-C Yang, H-P Kuo, Y-N Wang, H Yamaguchi, S A Miller & M-C Hung

  2. The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA

    Y Du, J Shen, C-C Yang, H-P Kuo & M-C Hung

  3. Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, Taiwan

    J L Hsu, Y-N Wang & M-C Hung

  4. Department of Biotechnology, Asia University, Taichung, Taiwan

    J L Hsu, Y-N Wang & M-C Hung

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Du, Y., Shen, J., Hsu, J. et al. Syntaxin 6-mediated Golgi translocation plays an important role in nuclear functions of EGFR through microtubule-dependent trafficking. Oncogene 33, 756–770 (2014). https://doi.org/10.1038/onc.2013.1

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