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首页> 外文期刊>Cellular Signalling >AGR3 promotes the sternness of colorectal cancer via modulating Wnt/beta-catenin signalling
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AGR3 promotes the sternness of colorectal cancer via modulating Wnt/beta-catenin signalling

机译：Agr3通过调节Wnt /β-catenin信号传导来促进结肠直肠癌的沉重

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摘要

Cancer cells with stem cell properties have been acknowledged to be responsible for cancer initiation and progression. Wnt/beta-catenin signalling is a major signal pathway promoting the sternness of cancer cells. Anterior gradient 3 (AGR3), a member of the protein disulfide isomerase (PDI) family, was found to be overexpressed in several cancers. However, the roles and mechanisms of AGR3 in colorectal cancer (CRC) have not been previously described. In our study, we find that AGR3 is highly expressed in CRC and associated with poor prognosis. Functional studies show that AGR3 promotes the sternness of CRC cells. Mechanically, AGR3 activates Wnt/beta-catenin signalling and promotes the nuclear translocation of beta-catenin to upregulate sternness related genes. Wnt/beta-catenin signalling inhibition counteracts the promoting effect of AGR3 on cancer sternness. Moreover, the effect of AGR3 on Wnt/beta-catenin signalling and cancer sternness depends on the presence of frizzled 4 (FZD4). Thus, our study first uncovers the stemness-promoting role and the oncogenic mechanism of AGR3 in CRC, which might provide a novel target for designing anti-CRC strategies.
机译：已经承认具有干细胞性质的癌细胞是癌症启动和进展的原因。 Wnt / beta-catenin信号传导是促进癌细胞损害的主要信号途径。在几种癌症中发现前梯度3（AgR3），蛋白二硫化物异构酶（PDI）家族的成员在过表达。然而，尚未描述结肠直肠癌（CRC）中AGR3中的作用和机制。在我们的研究中，我们发现Agr3在CRC中高度表达，并与预后差有关。功能研究表明，AGR3促进了CRC细胞的损伤。机械地，Agr3激活WNT /β-连环蛋白信号传导，促进β-连环蛋白的核转移以上调伤害相关基因。 WNT / Beta-catenin信号传导抑制抵消Agr3对癌症严厉的促进效果。此外，Agr3对Wnt /β - catenin信号传导和癌症静止的影响取决于毛毡4（FZD4）的存在。因此，我们的研究首先揭示了CRC中AGR3促进作用和致癌机制，这可能为设计反CRC策略提供了一种新的目标。

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  • 来源
    《Cellular Signalling》 |2020年第2020期|共10页
  • 作者

    Chi Jiangyang; Zhang Hongyan; Hu Jia; Song Yu; Li Jing; Wang Lin; Wang Zheng;

  • 作者单位

    Huazhong Univ Sci &

    Technol Union Hosp Tongji Med Coll Res Ctr Tissue Engn &

    Regenerat Med Wuhan 430022 Hubei Peoples R China;

    Huazhong Univ Sci &

    Technol Union Hosp Tongji Med Coll Res Ctr Tissue Engn &

    Regenerat Med Wuhan 430022 Hubei Peoples R China;

    Huazhong Univ Sci &

    Technol Union Hosp Tongji Med Coll Res Ctr Tissue Engn &

    Regenerat Med Wuhan 430022 Hubei Peoples R China;

    Huazhong Univ Sci &

    Technol Union Hosp Tongji Med Coll Res Ctr Tissue Engn &

    Regenerat Med Wuhan 430022 Hubei Peoples R China;

    Huazhong Univ Sci &

    Technol Union Hosp Tongji Med Coll Res Ctr Tissue Engn &

    Regenerat Med Wuhan 430022 Hubei Peoples R China;

    Huazhong Univ Sci &

    Technol Union Hosp Tongji Med Coll Res Ctr Tissue Engn &

    Regenerat Med Wuhan 430022 Hubei Peoples R China;

    Huazhong Univ Sci &

    Technol Union Hosp Tongji Med Coll Res Ctr Tissue Engn &

    Regenerat Med Wuhan 430022 Hubei Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞形态学;
  • 关键词

    AGR3; Wnt; beta-catenin; Cancer stemness; Colorectal cancer;

    机译：agr3;wnt;beta-catenin;癌症茎;结肠直肠癌;

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