Dept. of Biological Sciences, Towson University, 8000 York Rd, Towson, MD 21252, United States.
National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, United States.
Free Radic Biol Med. 2018 Nov 1;127:14-25. doi: 10.1016/j.freeradbiomed.2018.05.075. Epub 2018 May 22.
Selenocysteine-containing proteins (selenoproteins) have been implicated in the regulation of various cell signaling pathways, many of which are linked to colorectal malignancies. In this in-depth excurse into the selenoprotein literature, we review possible roles for human selenoproteins in colorectal cancer, focusing on the typical hallmarks of cancer cells and their tumor-enabling characteristics. Human genome studies of single nucleotide polymorphisms in various genes coding for selenoproteins have revealed potential involvement of glutathione peroxidases, thioredoxin reductases, and other proteins. Cell culture studies with targeted down-regulation of selenoproteins and studies utilizing knockout/transgenic animal models have helped elucidate the potential roles of individual selenoproteins in this malignancy. Those selenoproteins, for which strong links to development or progression of colorectal cancer have been described, may be potential future targets for clinical interventions.
含硒半胱氨酸的蛋白质(硒蛋白)被认为参与了多种细胞信号通路的调节,其中许多与结直肠恶性肿瘤有关。在对硒蛋白文献的深入研究中,我们综述了人类硒蛋白在结直肠癌中的可能作用,重点关注癌细胞的典型特征及其促进肿瘤发生的特征。对各种编码硒蛋白的基因中的单核苷酸多态性的人类基因组研究表明,谷胱甘肽过氧化物酶、硫氧还蛋白还原酶和其他蛋白质可能参与其中。通过靶向敲低硒蛋白的细胞培养研究和利用基因敲除/转基因动物模型的研究,有助于阐明个别硒蛋白在这种恶性肿瘤中的潜在作用。那些与结直肠癌的发生或发展有很强关联的硒蛋白,可能成为未来临床干预的潜在靶点。