Glycogen-specific kinase (GSK3β) is an integral regulator of the Wnt signalling pathway as well as many other diverse signalling pathways and processes. Dys-regulation of GSK3β is implicated in many different pathologies, including neurodegenerative disorders as well as many different tumour types. In the context of tumour development, GSK3β has been shown to play both oncogenic and tumour suppressor roles, depending upon tissue, signalling environment or disease progression. Although multiple substrates of the GSK3β kinase have been identified, the wider protein networks within which GSK3β participates are not well known, and the consequences of these interactions not well understood. In this study, LC-MS/MS expression analysis was performed using knockout GSK3β colorectal cancer cells and isogenic controls in colorectal cancer cell lines carrying dominant stabilizing mutations of β-Catenin. Consistent with the role GSK3β, we found that β-Catenin levels and canonical Wnt activity are unaffected by knockout of GSK3β and therefore use this knockout cell model to identify other processes in which GSK3β is implicated. Quantitative proteomic analysis revealed perturbation of proteins involved in cell-cell adhesion, and we characterize the phenotype and altered proteomic profiles associated with this. We also characterize the perturbation of metabolic pathways resulting from GSK3β knockout and identify defects in glycogen metabolism. In summary, using a precision colorectal cancer cell-line knockout model with constitutively activated β-Catenin we are able to identify several of the diverse pathways and processes associated with GSK3β function. p { margin-bottom: 0.25cm; direction: ltr; color: #00000a; line-height: 120%; text-align: left; orphans: 2; widows: 2 }p.western { font-family: "Times New Roman", serif }p.cjk { font-family: "PMingLiU", "????"; so-language: zh-CN }p.ctl { font-family: "Times New Roman"; font-size: 10pt }a:link { color: #0000ff }

中文翻译：

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GSK3β基因敲除的蛋白质组学表征显示结直肠癌细胞中细胞粘附和代谢途径利用的改变

糖原特异性激酶（GSK3β）是Wnt信号通路以及许多其他各种信号通路和过程的不可或缺的调节剂。GSK3β的Dys调节涉及许多不同的病理，包括神经退行性疾病以及许多不同的肿瘤类型。在肿瘤发展的背景下，GSK3β已显示出起致癌作用和抑癌作用，具体取决于组织，信号传导环境或疾病进展。尽管已鉴定出GSK3β激酶的多种底物，但GSK3β参与其中的更广泛的蛋白质网络尚不为人所知，并且这些相互作用的结果也未得到很好的理解。在这个研究中，使用敲除的GSK3β大肠癌细胞和携带β-Catenin显性稳定突变的大肠癌细胞系中的等基因对照进行LC-MS / MS表达分析。与GSK3β的作用一致，我们发现β-连环蛋白水平和经典Wnt活性不受GSK3β敲除的影响，因此使用此敲除细胞模型来鉴定涉及GSK3β的其他过程。定量蛋白质组学分析揭示了参与细胞间粘附的蛋白质的扰动，我们表征了与之相关的表型和改变的蛋白质组学特征。我们还表征了由GSK3β敲除引起的代谢途径的扰动，并鉴定了糖原代谢的缺陷。综上所述，使用具有组成性激活的β-Catenin的精确结直肠癌细胞系敲除模型，我们能够鉴定出与GSK3β功能相关的多种途径和过程。p {底边距：0.25厘米；方向：ltr; 颜色：＃00000a; 行高：120％；文字对齐：左；孤儿：2；寡妇：2} p.western {font-family：“ Times New Roman”，serif} p.cjk {font-family：“ PMingLiU”，“ ????”; 用法：zh-CN} p.ctl {font-family：“时代新罗马书”；字体大小：10pt} a：link {颜色：＃0000ff} “ PMingLiU”，“ ????”; 用法：zh-CN} p.ctl {font-family：“时代新罗马书”；字体大小：10pt} a：link {颜色：＃0000ff} “ PMingLiU”，“ ????”; 用法：zh-CN} p.ctl {font-family：“时代新罗马书”；字体大小：10pt} a：link {颜色：＃0000ff}