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Chemosensitization of prostate cancer stem cells in mice by angiogenin and plexin-B2 inhibitors.
Communications Biology ( IF 5.9 ) Pub Date : 2020-01-15 , DOI: 10.1038/s42003-020-0750-6
Shuping Li 1 , Kevin A Goncalves 1, 2 , Baiqing Lyu 1 , Liang Yuan 1, 3 , Guo-Fu Hu 1, 2, 3
Affiliation  

Cancer stem cells (CSCs) are an obstacle in cancer therapy and are a major cause of drug resistance, cancer recurrence, and metastasis. Available treatments, targeting proliferating cancer cells, are not effective in eliminating quiescent CSCs. Identification of CSC regulators will help design therapeutic strategies to sensitize drug-resistant CSCs for chemo-eradication. Here, we show that angiogenin and plexin-B2 regulate the stemness of prostate CSCs, and that inhibitors of angiogenin/plexin-B2 sensitize prostate CSCs to chemotherapy. Prostate CSCs capable of self-renewal, differentiation, and tumor initiation with a single cell inoculation were identified and shown to be regulated by angiogenin/plexin-B2 that promotes quiescence and self-renewal through 5S ribosomal RNA processing and generation of the bioactive 3'-end fragments of 5S ribosomal RNA, which suppress protein translation and restrict cell cycling. Monoclonal antibodies of angiogenin and plexin-B2 decrease the stemness of prostate CSCs and sensitize them to chemotherapeutic agents in vitro and in vivo.

中文翻译:

血管生成素和plexin-B2抑制剂对小鼠前列腺癌干细胞的化学增敏作用。

癌症干细胞(CSC)是癌症治疗的障碍,并且是耐药性,癌症复发和转移的主要原因。针对增殖的癌细胞的可用治疗方法无法有效消除静止的CSC。CSC调节剂的鉴定将有助于设计治疗策略,以使耐药CSC敏感化为化学根。在这里,我们显示血管生成素和plexin-B2调节前列腺CSC的干性,并且血管生成素/ plexin-B2的抑制剂使前列腺CSC对化学疗法敏感。鉴定出能够通过单细胞接种实现自我更新,分化和肿瘤萌发的前列腺CSC,并显示其受血管生成素/丛蛋白B2的调节,血管生成素/丛蛋白B2通过5S核糖体RNA加工和生物活性3'的产生促进静止和自我更新。5S核糖体RNA的末端片段,可抑制蛋白质翻译并限制细胞周期。血管生成素和plexin-B2的单克隆抗体可降低前列腺CSC的干性,并在体外和体内使它们对化学治疗剂敏感。
更新日期:2020-01-15
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