Protein kinase D2-Aurora kinase A-ERK1/2 signalling axis drives neuroendocrine differentiation of epithelial ovarian cancer

被引：2

作者：

Sachdeva, Abha ^{[1
]}

Roy, Adhiraj ^{[1
]}

Mandal, Supratim ^{[2
]}

机构：

[1] Amity Univ, Amity Inst Mol Med & Stem Cell Res, Sect 125, Noida 201303, Uttar Pradesh, India

[2] Univ Kalyani, Dept Microbiol, Kalyani 741235, W Bengal, India

来源：

MOLECULAR AND CELLULAR BIOCHEMISTRY | 2025年 / 480卷 / 01期

关键词：

Epithelial ovarian cancer; Neuroendocrine differentiation; Protein kinase D2; Aurora kinase A; Chemoresistance; Cancer cell signalling; PROSTATE-CANCER;

D O I：

10.1007/s11010-024-04986-2

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：535 / 547

页数：13

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