Nat Commun:ONECUT2是神经内分泌前列腺癌的驱使因子

2019-01-28 AlexYang MedSci原创

神经内分泌前列腺癌(NEPC)是一种致死性的疾病,可以通过雄激素受体(AR)信号在神经内分泌分化过程中的缺失来鉴定。临床上、基因组水平上和表观遗传水平上来讲,NEPC类似于其他类型的低分化程度的神经内分泌肿瘤(NETs)。最近,有研究人员通过pan-NET分析,鉴定了ONECUT2可以作为低分化NETs的候选主要转录调控因子。ONECUT2在前列腺恶性肿瘤中的异位表达能够与缺氧协同来抑制雄激素信号

神经内分泌前列腺癌(NEPC)是一种致死性的疾病,可以通过雄激素受体(AR)信号在神经内分泌分化过程中的缺失来鉴定。临床上、基因组水平上和表观遗传水平上来讲,NEPC类似于其他类型的低分化程度的神经内分泌肿瘤(NETs)。

最近,有研究人员通过pan-NET分析,鉴定了ONECUT2可以作为低分化NETs的候选主要转录调控因子。ONECUT2在前列腺恶性肿瘤中的异位表达能够与缺氧协同来抑制雄激素信号,并诱导神经内分泌的可塑性。ONECUT2能够在NEPC中促使肿瘤的恶化,部分的是通过调控缺氧信号好肿瘤缺氧来实现的。特别的是,ONECUT2能够激活SMAD3,从而通过调节HIF1α染色质的结合来调控缺氧信号,从而导致NEPC与前列腺癌比较表现出更高等级的缺氧情况。另外,利用缺氧激活前体药物TH-302治疗能够减少NEPC肿瘤的生长。

最后,研究人员指出,他们的结果强调了 OENCUT2与缺氧在促使NEPC中的协同作用,并且指出了直接进行靶向缺氧的治疗在NEPC患者治疗中的潜力。

原始出处:

Haiyang Guo, Xinpei Ci, Musaddeque Ahmed et al. ONECUT2 is a driver of neuroendocrine prostate cancer. Nat Commun. 17 January 2019.

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    2019-03-04 gwc392
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