This study focuses on the role of lysosomal trafficking in prostate cancer, given the essential role of lysosomes in cellular homoeostasis.
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.
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.
These findings provide novel insights into the altered regulation and functional impact of lysosomal vesicular trafficking in prostate cancer pathogenesis.
British journal of cancer. 2024 Aug 31 [Epub]
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, Ian R D Johnson
Mechanisms in Cell Biology and Diseases Research Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia. ., Placental Cell Biology Group, National Institute of Environmental Health and Science, National Institutes of Health, Research Triangle Park, NC, 27709, USA., Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK., Mechanisms in Cell Biology and Diseases Research Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Quality Use of Medicines and Pharmacy Research Centre, University of South Australia City East Campus, Frome Rd, Adelaide, SA, 5000, Australia., Centre for Cancer Biology, University of South Australia, Adelaide, SA, 5000, Australia., South Australian ImmunoGENomics Cancer Institute and Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, 5000, Australia., Department of Histopathology, Trinity College Dublin, Dublin, Dublin 8, Ireland., Mechanisms in Cell Biology and Diseases Research Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia. .