Associação Portuguesa de Investigação em Cancro
Peroxisomes are involved in malignant transformation in prostate cancer
Peroxisomes are involved in malignant transformation in prostate cancer
Monocarboxylate transporter 2 (MCT2) is overexpressed in prostate malignant glands, pointing it out as a putative biomarker for prostate cancer. In this study, it was demonstrated that MCT2 localizes mainly at peroxisomes in prostate cancer cells and is able to take advantage of the peroxisomal transport machinery. It was also shown an increase in MCT2 expression from non-malignant to malignant cells that was directly correlated with its peroxisomal localization. Upon analysis of the expression of several peroxisomal β-oxidation, it was shown that MCT2 presence at peroxisomes is related to an increase in β-oxidation levels which may be crucial for malignant transformation. Our results present novel evidence that may not only contribute to the study of prostate cancer development mechanisms but also pinpoint novel targets for cancer therapy.
Authors and affiliations:
Isabel Valença a, #, Nelma Pértega-Gomes b, c, #, José Rámon Vizcaino d, Rui M. Henrique e, f, g,
Carlos Lopes d, Fátima Baltazar b, c, §, Daniela Ribeiro a, §.
a Centre for Cell Biology and Department of Biology, University of Aveiro, Aveiro, Portugal
b Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
c ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimar~aes, Portugal
d Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal
e Cancer Epigenetics Group-Research Centre, Portuguese Oncology Institute, Porto, Portugal
f Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences, University of Porto, Porto, Portugal
g Department of Pathology, Portuguese Oncology Institute, Porto, Portugal
#,§Equal contribution
Abstract:
Previous studies on monocarboxylate transporters expression in prostate cancer (PCa) have shown that monocarboxylate transporter 2 (MCT2) was clearly overexpressed in prostate malignant glands, pointing it out as a putative biomarker for PCa. However, its localization and possible role in PCa cells remained unclear. In this study, we demonstrate that MCT2 localizes mainly at peroxisomes in PCa cells and is able to take advantage of the peroxisomal transport machinery by interacting with Pex19. We have also shown an increase in MCT2 expression from non-malignant to malignant cells that was directly correlated with its peroxisomal localization. Upon analysis of the expression of several peroxisomal β-oxidation proteins in PIN lesions and PCa cells from a large variety of human prostate samples, we suggest that MCT2 presence at peroxisomes is related to an increase in β -oxidation levels which may be crucial for malignant transformation. Our results present novel evidence that may not only contribute to the study of PCa development mechanisms but also pinpoint novel targets for cancer therapy.
Journal: Journal of Cellular and Molecular Medicine
