在结肠癌中,通过糖基化WNT/ β - catenin信号通路,ALG8为干细胞提供燃料。

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xianqiu Wu, Bin Wang, Yaorong Su, Dongtian He, Haixin Mo, Mingzhu Zheng, Zijie Meng, Liangliang Ren, Xin Zhang, Dong Ren, Chao Li
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引用次数: 1

摘要

肿瘤干细胞(CSCs)驱动肿瘤复发是结肠癌的主要临床挑战。靶向干细胞为根除癌细胞从而治疗癌症患者提供了巨大的机会。然而,结肠癌中CSC信号和关键分子的表观遗传控制尚不清楚。在本研究中,我们证明了α -1,3-葡萄糖基转移酶(ALG8)在结肠癌组织中与正常组织相比表达上调。在结肠癌患者中,ALG8基因的过表达预示着较差的总生存率和无病生存率。沉默ALG8基因可抑制结肠肿瘤细胞的干性。与对照小鼠相比,移植了缺乏alg8肿瘤细胞的异种移植小鼠的肿瘤负荷明显减轻,生存期延长。进一步分析表明,ALG8基因通过诱导LRP6的糖基化,激活WNT/ β -catenin信号通路,从而促进肿瘤的发生。重要的是,tunicamycin对糖基化的抑制消除了ALG8基因对肿瘤发生的影响。综上所述,我们的研究结果表明,ALG8通过激活WNT/ β -连环蛋白信号通路来促进结肠肿瘤的发生。因此,ALG8基因是结肠癌潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ALG8 Fuels Stemness Through Glycosylation of the WNT/Beta-Catenin Signaling Pathway in Colon Cancer.

Cancer stem cells (CSCs) drive tumor relapse, which is a major clinical challenge in colon cancer. Targeting CSCs presents a great opportunity in eradicating cancer cells and thus treatment of patients with cancer. However, the epigenetic control of the CSC signature and key molecules involved in colon cancer remains undefined. In this study, we demonstrated that alpha-1,3-glucosyltransferase (ALG8) is upregulated in colon cancer tissues compared with normal tissues. Overexpression of the ALG8 gene predicted poor overall survival and disease-free survival in colon cancer patients. Silencing of the ALG8 gene repressed the stemness of colon tumor cells. Xenograft mice transplanted with ALG8-deficient tumor cells significantly alleviated tumor burden and prolonged survival in comparison with control mice. Further analysis showed that ALG8 gene promoted cancer stemness through inducing glycosylation of LRP6, which activates the WNT/beta-catenin signaling pathway. Importantly, attenuation of the glycosylation using tunicamycin abrogated the effect of ALG8 gene on cancer stemness. Taken together, our findings demonstrated that ALG8 enhances colon tumorigenesis by activating the WNT/beta-catenin signaling pathway. Therefore, ALG8 gene is a potential therapeutic target in colon cancer.

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来源期刊
DNA and cell biology
DNA and cell biology 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
93
审稿时长
1.5 months
期刊介绍: DNA and Cell Biology delivers authoritative, peer-reviewed research on all aspects of molecular and cellular biology, with a unique focus on combining mechanistic and clinical studies to drive the field forward. DNA and Cell Biology coverage includes: Gene Structure, Function, and Regulation Gene regulation Molecular mechanisms of cell activation Mechanisms of transcriptional, translational, or epigenetic control of gene expression Molecular Medicine Molecular pathogenesis Genetic approaches to cancer and autoimmune diseases Translational studies in cell and molecular biology Cellular Organelles Autophagy Apoptosis P bodies Peroxisosomes Protein Biosynthesis and Degradation Regulation of protein synthesis Post-translational modifications Control of degradation Cell-Autonomous Inflammation and Host Cell Response to Infection Responses to cytokines and other physiological mediators Evasive pathways of pathogens.
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