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Overexpression of myosin VI in prostate cancer cells enhances PSA and VEGF secretion, but has no effect on endocytosis

Oncogene volume 29, pages 188–200 (2010)Cite this article

Abstract

Tissue expression microarrays, employed to determine the players and mechanisms leading to prostate cancer development, have consistently shown that myosin VI, a unique actin-based motor, is upregulated in medium-grade human prostate cancers. Thus, to understand the role of myosin VI in prostate cancer development, we have characterized its intracellular localization and function in the prostate cancer cell line LNCaP. Using light and electron microscopy, we identified myosin VI on Rab5-positive early endosomes, as well as on recycling endosomes and the trans-Golgi network. Intracellular targeting seems to involve two myosin VI-interacting proteins, GIPC and LMTK2, both of which can be co-immunoprecipitated with myosin VI from LNCaP cells. The absence of Disabled-2 (Dab2), a tumour suppressor and myosin VI-binding partner, inhibits recruitment of myosin VI to endocytic structures at the plasma membrane in LNCaP cells, but interestingly has no effect on endocytosis. Small interfering RNA-mediated downregulation of myosin VI expression results in a significant reduction in prostate-specific antigen (PSA) and vascular endothelial growth factor (VEGF) secretion in LNCaP cells. Our results suggest that in prostate cancer cells, myosin VI regulates protein secretion, but the overexpression of myosin VI has no major impact on clathrin-mediated endocytosis.

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Acknowledgements

We thank A Peden for help with transferrin uptake assays and JP Luzio for helpful discussions. This work was funded by the Cancer Research UK project grant (CP), the Wellcome Trust Senior Fellowship (to FB), the Wellcome Trust PhD studentship (AJK) and was supported by the Medical Research Council. CIMR is in receipt of a strategic award from the Wellcome Trust.

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  1. Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge, UK

    C Puri, M V Chibalina, S D Arden, A J Kruppa & F Buss

  2. MRC Laboratory of Molecular Biology, Cambridge, UK

    J Kendrick-Jones

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  1. C Puri
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  2. M V Chibalina
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  3. S D Arden
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Correspondence to F Buss.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Puri, C., Chibalina, M., Arden, S. et al. Overexpression of myosin VI in prostate cancer cells enhances PSA and VEGF secretion, but has no effect on endocytosis. Oncogene 29, 188–200 (2010). https://doi.org/10.1038/onc.2009.328

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