Division of Nephrology, Department of Internal Medicine, University of California, Davis, CA.
Semin Nephrol. 2020 Jan;40(1):14-27. doi: 10.1016/j.semnephrol.2019.12.003.
Clear cell renal cell carcinoma (ccRCC) is a major cancer yet has long evaded extensive efforts to target it chemotherapeutically. Recent efforts to characterize its proteome and metabolome in a grade-defined manner has resulted in a global proteometabolomic reprogramming model yielding a number of potential drug targets, many of which are under the control of transcription factor and MYC proto-oncogene, bHLH transcription factor. Furthermore, through the use of conventional technologies such as immunohistochemistry, protein moonlighting, a phenomenon wherein a single protein performs more than one distinct biochemical or biophysical functions, is emerging as a second mode of operation for ccRCC metabolo-proteomic reprogramming. This renders the subcellular localization of the grade-defining biomarkers an additional layer of grade-defining ccRCC molecular signature, although its functional significance in ccRCC etiology is only beginning to emerge.
透明细胞肾细胞癌（ccRCC）是一种主要的癌症，但长期以来一直难以通过化疗靶向治疗。最近，人们以分级定义的方式对其蛋白质组和代谢组进行了特征描述，这导致了一个全面的蛋白质代谢组重编程模型，产生了许多潜在的药物靶点，其中许多靶点受转录因子和 MYC 原癌基因、bHLH 转录因子的控制。此外，通过使用免疫组织化学等传统技术，蛋白质兼职（一种单个蛋白质执行不止一种不同的生化或物理功能的现象）正在成为 ccRCC 代谢组-蛋白质组重编程的第二种操作模式。这使得分级定义生物标志物的亚细胞定位成为了分级定义 ccRCC 分子特征的另一个层次，尽管其在 ccRCC 病因学中的功能意义才刚刚开始显现。
