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CITED2 的异常表达通过激活核仁素-AKT 通路促进前列腺癌转移。

Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nucleolin-AKT pathway.

机构信息

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.

出版信息

Nat Commun. 2018 Oct 5;9(1):4113. doi: 10.1038/s41467-018-06606-2.

DOI:10.1038/s41467-018-06606-2
PMID:30291252
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6173745/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/dabae0ff8fe4/41467_2018_6606_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/39318c0c1eeb/41467_2018_6606_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/66f0a219accd/41467_2018_6606_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/2664403318e6/41467_2018_6606_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/ea2febf2ce87/41467_2018_6606_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/c73bbbc62791/41467_2018_6606_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/40fa019d7908/41467_2018_6606_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/dabae0ff8fe4/41467_2018_6606_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/39318c0c1eeb/41467_2018_6606_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/66f0a219accd/41467_2018_6606_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/2664403318e6/41467_2018_6606_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/ea2febf2ce87/41467_2018_6606_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/c73bbbc62791/41467_2018_6606_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/40fa019d7908/41467_2018_6606_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/6173745/dabae0ff8fe4/41467_2018_6606_Fig7_HTML.jpg

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