The functional landscape of Golgi membrane protein 1 (GOLM1) phosphoproteome reveal GOLM1 regulating P53 that promotes malignancy.
The functional landscape of Golgi membrane protein 1 (GOLM1) phosphoproteome reveal GOLM1 regulating P53 that promotes malignancy.
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高尔基膜蛋白1（GOLM1）的磷蛋白组的功能景观揭示了调节促进恶性肿瘤的p53的GOLM1。
DOI：
10.1038/s41420-021-00422-2
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发表时间：
2021-03-01
影响因子：
7
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Song Q;He X;Xiong Y;Wang J;Zhang L;Leung EL;Li G
高尔基体膜蛋白1（Golgi membrane protein 1，GOLM 1）与多种癌症的发生有关。然而，肺癌中GOLM 1过表达的磷酸化蛋白质组景观在很大程度上仍然未知。本研究利用癌症基因组图谱（TCGA）和磷酸化蛋白质组数据，系统评价GOLM 1基因的功能，并研究其在非小细胞肺癌（NSCLC）中的预后价值。用Trans-well系统检测GOLM 1过表达的PC 9细胞的增殖、迁移和侵袭能力。在小鼠模型中观察肿瘤移植物并通过离体证实。在TCGA数据库中，GOLM 1表达增加的NSCLC患者的总生存期（OS）较短。GOLM 1在肿瘤粘附连接、细胞周期和通路相关单基因集富集分析（GSEA）中的应用GOLM 1在GOLM 1 OE PC 9细胞中的过表达促进细胞增殖、迁移和侵袭。在迁移实验中，在GOLM 1 KD PC 9细胞中，在GOLM 1敲低中也观察到迁移和侵袭潜力降低。GOLM 1的表达增加可显著增加异种移植瘤小鼠模型中的肿瘤生长。磷酸化蛋白质组分析显示GOLM 1 OE PC 9细胞中有239个磷酸化蛋白上调，331个磷酸化蛋白下调。GOLM 1在GSEA中的过表达与MAPK信号通路中的P53密切相关。GOLM 1的过表达增强了P53蛋白在S315位点的磷酸化，但抑制了P53四聚体的形成。这些结果表明GOLM 1过表达通过抑制P53四聚体的形成而增强非小细胞癌的侵袭性。
Golgi membrane protein 1 (GOLM1) was implicated in carcinogenesis of multiple types of cancer. However, Phosphoproteome landscapes of GOLM1 overexpression in lung cancer remain largely unknown. In this study, using data from the Cancer Genome Atlas (TCGA) and phosphoproteome, we systematically evaluated the feature of GOLM1 and studied its prognostic value in non-small cell lung cancer (NSCLC). The proliferation, migration, and invasion capacities in PC9 cell with GOLM1 overexpression were determined using Trans-well system assay. Tumor engrafts was visualized in mice models and confirmed by ex vivo. An increased expression of GOLM1 had shorter overall survival (OS) in patients with NSCLC in TCGA database. GOLM1 in single gene set enrichment analysis (GSEA) related to adherent’s junction, cell cycle, and pathway in cancer. Overexpression of GOLM1 in GOLM1OE PC9 cells promoted cell proliferation, migration, and invasion. Decreased migration and invasion potential were also observed in knockdown of GOLM1 in GOLM1KD PC9 cells in migration assay. An increased expression of GOLM1 could significantly increase the growth of tumor in xenograft mice models. phosphoproteome analysis showed 239 upregulated and 331 downregulated Phosphorylated proteins in GOLM1OE PC9 cells. Overexpression of GOLM1 in GSEA was significantly related to P53 in MAPK signaling pathway. Overexpression of GOLM1enhanced the phosphorylation of P53 protein at site S315 but inhibited the formation of P53 tetramers. These results indicate that overexpression GOLM1 enhances non-small-cell carcinoma aggressiveness through inhibited the formation of P53 tetramer.
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影响因子：
50.3
作者：
Ye QH;Zhu WW;Zhang JB;Qin Y;Lu M;Lin GL;Guo L;Zhang B;Lin ZH;Roessler S;Forgues M;Jia HL;Lu L;Zhang XF;Lian BF;Xie L;Dong QZ;Tang ZY;Wang XW;Qin LX
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DOI：
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期刊：
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影响因子：
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作者：
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通讯作者：
Colditz GA
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影响因子：
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作者：
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