Valença Isabel, Pértega-Gomes Nelma, Vizcaino José Rámon, Henrique Rui M, Lopes Carlos, Baltazar Fátima, Ribeiro Daniela
Centre for Cell Biology and Department of Biology, University of Aveiro, Aveiro, Portugal.
J Cell Mol Med. 2015 Apr;19(4):723-33. doi: 10.1111/jcmm.12481. Epub 2015 Jan 30.
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.
先前关于前列腺癌（PCa）中一元羧酸转运体表达的研究表明，一元羧酸转运体2（MCT2）在前列腺恶性腺体中明显过表达，表明它是PCa的一种潜在生物标志物。然而，其在PCa细胞中的定位及其可能的作用仍不清楚。在本研究中，我们证明MCT2主要定位于PCa细胞的过氧化物酶体，并能够通过与Pex19相互作用利用过氧化物酶体转运机制。我们还表明，从非恶性细胞到恶性细胞，MCT2表达增加，这与其过氧化物酶体定位直接相关。在分析来自大量人类前列腺样本的PIN病变和PCa细胞中几种过氧化物酶体β氧化蛋白的表达后，我们认为过氧化物酶体中MCT2的存在与β氧化水平的增加有关，这可能对恶性转化至关重要。我们的结果提供了新的证据，这不仅可能有助于PCa发生机制的研究，还能确定癌症治疗的新靶点。
