Protein modifications throughout the lung cancer proteome unravel the cancer-specific regulation of glycolysis
Protein modifications throughout the lung cancer proteome unravel the cancer-specific regulation of glycolysis
复制标题
整个肺癌蛋白质组的蛋白质修饰揭示了糖酵解的癌症特异性调节
DOI：
10.1016/j.celrep.2021.110137
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发表时间：
2021-12-21
期刊：
影响因子：
8.8
通讯作者：
Wei, Guangwei
中科院分区：
文献类型：
--
作者：
Duan, Yangmiao;Li, Jingyi;Wei, Guangwei
糖酵解重编程是癌症的一个典型特征。然而，糖酵解酶的癌症特异性调节需要系统的阐明。在这里，我们通过在蛋白质组学尺度上系统地鉴定人类非小细胞肺癌中的δ团块，报告了一系列与糖酵解途径特异性相关的酶家族的失调修饰。最显著的修饰是三磷酸异构酶（TPI）第58号丝氨酸（Ser58）上的δ质量为79.967 Da，这被证实是磷酸化。阻断TPI Ser58磷酸化可显著抑制糖酵解、肿瘤生长和转移。蛋白激酶PRKACA直接磷酸化TPI Ser58，从而增强TPI酶活性和糖酵解。在各种人类肿瘤标本中检测到TPI Ser58磷酸化的上调，并与不良生存率相关。因此，我们的研究确定了一些跨越糖酵解酶的癌症特异性蛋白质修饰，并揭示了TPI Ser58磷酸化在糖酵解和肺癌发展中的意义。
Glycolytic reprogramming is a typical feature of cancer. However, the cancer-specific modulation of glycolytic enzymes requires systematic elucidation. Here, we report a range of dysregulated modifications in association with a family of enzymes specifically related to the glycolysis pathway by systematic identification of delta masses at the proteomic scale in human non-small-cell lung cancer. The most significant modification is the delta mass of 79.967 Da at serine 58 (Ser58) of triosephosphate isomerase (TPI), which is confirmed to be phosphorylation. Blocking TPI Ser58 phosphorylation dramatically inhibits glycolysis, cancer growth, and metastasis. The protein kinase PRKACA directly phosphorylates TPI Ser58, thereby enhancing TPI enzymatic activity and glycolysis. The upregulation of TPI Ser58 phosphorylation is detected in various human tumor specimens and correlates with poor survival. Therefore, our study identifies a number of cancer-specific protein modifications spanned on glycolytic enzymes and unravels the significance of TPI Ser58 phosphorylation in glycolysis and lung cancer development.