Altered expression of vesicular trafficking machinery in prostate cancer affects lysosomal dynamics and provides insight into the underlying biology and disease progression
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(Published version)
Date
2024
Authors
Nturubika, B.D.
Guardia, C.M.
Gershlick, D.C.
Logan, J.M.
Martini, C.
Heatlie, J.K.
Lazniewska, J.
Moore, C.
Lam, G.T.
Li, K.L.
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Journal article
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British Journal of Cancer, 2024; 131(8):1263-1278
Statement of Responsibility
Bukuru D. Nturubika, Carlos M. Guardia, David C. Gershlick, Jessica M. Logan, Carmela Martini, Jessica K. Heatlie, Joanna Lazniewska, Courtney Moore, Giang T. Lam, Ka L. Li, Ben S-Y Ung, Robert D. Brooks, Shane M. Hickey, Andrew G. Bert, Philip A. Gregory, Lisa M. Butler, John J. O, Leary, Douglas A. Brooks, and Ian R. D. Johnson
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Abstract
BACKGROUND: This study focuses on the role of lysosomal trafficking in prostate cancer, given the essential role of lysosomes in cellular homoeostasis. METHODS: Lysosomal motility was evaluated using confocal laser scanning microscopy of LAMP-1-transfected prostate cells and spot-tracking analysis. Expression of lysosomal trafficking machinery was evaluated in patient cohort databases and through immunohistochemistry on tumour samples. The roles of vesicular trafficking machinery were evaluated through over-expression and siRNA. The effects of R1881 treatment on lysosome vesicular trafficking was evaluated by RNA sequencing, protein quantification and fixed- and live-cell microscopy. RESULTS: Altered regulation of lysosomal trafficking genes/proteins was observed in prostate cancer tissue, with significant correlations for co-expression of vesicular trafficking machinery in Gleason patterns. The expression of trafficking machinery was associated with poorer patient outcomes. R1881 treatment induced changes in lysosomal distribution, number, and expression of lysosomal vesicular trafficking machinery in hormone-sensitive prostate cancer cells. Manipulation of genes involved in lysosomal trafficking events induced changes in lysosome positioning and cell phenotype, as well as differential effects on cell migration, in non-malignant and prostate cancer cells. CONCLUSIONS: These findings provide novel insights into the altered regulation and functional impact of lysosomal vesicular trafficking in prostate cancer pathogenesis.
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Data source: Data availability, https://doi.org/10.1038/s41416-024-02829-x
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© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by/4.0/.