Epithelial ovarian cancer (EOC) is deadliest gynecological malignancy with poor prognosis and patient survival. Despite development of several therapeutic interventions such as poly-ADP ribose polymerase (PARP) inhibitors, EOC remains unmanageable and discovery of novel early detection biomarkers and treatment targets are highly warranted. Although neuroendocrine differentiation (NED) is implicated in different human cancers including prostate adenocarcinoma and lung cancer, mechanistic studies concerning NED of epithelial ovarian cancer are lacking. We report that Aurora kinase A drives NED of epithelial ovarian cancer in an ERK1/2-dependent manner and pharmacological and genetic inhibition of Aurora kinase A suppress NED of ovarian cancer. Moreover, we demonstrate that protein kinase D2 positively regulated Aurora kinase A to drive NED. Overexpression of catalytically active PKD2 drives NED and collectively, PKD2 cross talks with Aurora kinase A/ERK1/2 signalling axis to positively regulate NED of EOC. PKD2/Aurora kinase A/ERK1/2 signalling axis is a novel therapeutic target against neuroendocrine differentiated EOC.

上皮性卵巢癌（EOC）是最致命的妇科恶性肿瘤，预后和患者生存率均较差。尽管开发了多种治疗干预措施，例如聚 ADP 核糖聚合酶 (PARP) 抑制剂，但 EOC 仍然难以控制，因此非常有必要发现新型早期检测生物标志物和治疗靶点。尽管神经内分泌分化（NED）与包括前列腺腺癌和肺癌在内的不同人类癌症有关，但缺乏关于上皮性卵巢癌NED的机制研究。我们报道极光激酶 A 以 ERK1/2 依赖性方式驱动上皮性卵巢癌的 NED，并且极光激酶 A 的药理和遗传抑制可抑制卵巢癌的 NED。此外，我们证明蛋白激酶 D2 正向调节 Aurora 激酶 A 来驱动 NED。催化活性 PKD2 的过度表达可驱动 NED，并且 PKD2 与 Aurora 激酶 A/ERK1/2 信号轴相互作用，从而正向调节 EOC 的 NED。 PKD2/极光激酶 A/ERK1/2 信号轴是针对神经内分泌分化 EOC 的新型治疗靶点。