Department of Biomedical Science, BK21-plus Education Program, Seoul National University College of Medicine, Seoul, Korea.
Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.
Nat Commun. 2018 Oct 5;9(1):4113. doi: 10.1038/s41467-018-06606-2.
Despite many efforts to develop hormone therapy and chemotherapy, no effective strategy to suppress prostate cancer metastasis has been established because the metastasis is not well understood. We here investigate a role of CBP/p300-interacting transactivator with E/D-rich carboxy-terminal domain-2 (CITED2) in prostate cancer metastasis. CITED2 is highly expressed in metastatic prostate cancer, and its expression is correlated with poor survival. The CITED2 gene is highly activated by ETS-related gene that is overexpressed due to chromosomal translocation. CITED2 acts as a molecular chaperone to guide PRMT5 and p300 to nucleolin, thereby activating nucleolin. Informatics and experimental data suggest that the CITED2-nucleolin axis is involved in prostate cancer metastasis. This axis stimulates cell migration through the epithelial-mesenchymal transition and promotes cancer metastasis in a xenograft mouse model. Our results suggest that CITED2 plays a metastasis-promoting role in prostate cancer and thus could be a target for preventing prostate cancer metastasis.
尽管人们努力开发激素治疗和化疗方法，但由于对转移机制的了解有限，仍未确立有效的抑制前列腺癌转移的策略。我们在此研究 CBP/p300 相互作用转录激活因子与富含 E/D 的羧基末端域-2（CITED2）在前列腺癌转移中的作用。CITED2 在转移性前列腺癌中高表达，其表达与预后不良相关。由于染色体易位导致 ETS 相关基因过表达，从而高度激活 CITED2 基因。CITED2 作为一种分子伴侣，指导 PRMT5 和 p300 与核仁蛋白结合，从而激活核仁蛋白。信息学和实验数据表明，CITED2-核仁蛋白轴参与了前列腺癌的转移。该轴通过上皮-间充质转化刺激细胞迁移，并在异种移植小鼠模型中促进癌症转移。我们的研究结果表明，CITED2 在前列腺癌中发挥促进转移的作用，因此可能成为预防前列腺癌转移的靶点。
Zotero 插件
