核受体共激活因子3在肿瘤中的作用

The roles of nuclear receptor coactivator-3 in cancer

核受体共激活因子3(NCOA3)属于p160类固醇受体共激活因子(SRC)家族,具有激活不同核受体的功能,例如参与类固醇、类维生素、甲状腺激素、维生素D3和前列腺素等的共激活。研究显示,NCOA3可通过染色质的重塑在创建多亚基共激活因子复合物中起着核心作用,显示组蛋白乙酰转移酶活性。在激素刺激核受体的情况下,NCOA3与其他转录因子共同激活基因转录,在正常生理中发挥重要作用。越来越多的研究表明,在乳腺癌、胰腺癌、肝癌和骨髓瘤等癌症中,过表达的NCOA3对肿瘤生长、侵袭、转移和化疗耐药性等过程有着重要影响。该文主要就NCOA3在肿瘤中的表达水平、在致癌机制中参与的信号通路以及在肿瘤多药耐药性机制中的作用等最新研究进展作一综述,希望为肿瘤的诊断、治疗与预后监测提供新思路。

Nuclear receptor coactivator-3(NCOA3),which is involved in the coactivation of different nuclear receptors,such as steroids(GR and ER),retinoids(RARs and RXRs),thyroid hormone(TRs),vitamin D3(VDR)and prostanoids(PPARs),belongs to the SRC/p160 nuclear receptor coactivator family.Studies show NCOA3,via remodeling of chromatin,plays a central role in creating a multisubunit coactivator complex and displays histone acetyltransferase activity.In the case of hormone stimulation of nuclear receptors,NCOA3 is involved in the co-activation of gene transcription with other transcription factors and plays an important role in normal physiology.More and more researches suggest NCOA3 overexpression has a significant impact on cancer growth,invasion,metastasis and chemotherapy resistance and other processes,such as breast cancer,pancreatic cancer,liver cancer,and myeloma,etc.Here,we provide an overview of the roles of NCOA3 in cancer growth,carcinogenic signaling pathways,and tumor multi-drug resistance,hoping to provide new ideas for the diagnosis,treatment and prognosis monitoring of cancers.