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Localization of MCT2 at peroxisomes is associated with malignant transformation in prostate cancer

机译:MCT2在过氧化物酶体的定位与前列腺癌的恶性转化有关

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摘要

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 ß-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 ß -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.
机译:先前对前列腺癌(PCa)中单羧酸盐转运蛋白表达的研究表明,单羧酸盐转运蛋白2(MCT2)在前列腺恶性腺中明显过表达,指出它是PCa的公认生物标记。但是,其定位及其在PCa细胞中的可能作用仍不清楚。在这项研究中,我们证明了MCT2主要位于PCa细胞中的过氧化物酶体,并能够通过与Pex19相互作用利用过氧化物酶体转运机制。我们还显示了MCT2表达从非恶性细胞到恶性细胞的增加,这与其过氧化物酶体局部定位直接相关。通过分析多种人前列腺样品的PIN损伤和PCa细胞中几种过氧化物酶体ß-氧化蛋白的表达,我们建议过氧化物酶体中MCT2的存在与ß-氧化水平的升高有关,这可能对恶性肿瘤至关重要转型。我们的结果提供了新颖的证据,这些证据不仅可能有助于PCa发育机制的研究,而且可以查明癌症治疗的新靶标。

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