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cAMP 依赖性信号转导与卵巢癌。

cAMP-Dependent Signaling and Ovarian Cancer.

机构信息

Department of Anatomy and Histology, Collegium Medicum, University of Zielona Gora, 65-046 Zielona Gora, Poland.

出版信息

Cells. 2022 Nov 29;11(23):3835. doi: 10.3390/cells11233835.

Abstract

cAMP-dependent pathway is one of the most significant signaling cascades in healthy and neoplastic ovarian cells. Working through its major effector proteins-PKA and EPAC-it regulates gene expression and many cellular functions. PKA promotes the phosphorylation of cAMP response element-binding protein (CREB) which mediates gene transcription, cell migration, mitochondrial homeostasis, cell proliferation, and death. EPAC, on the other hand, is involved in cell adhesion, binding, differentiation, and interaction between cell junctions. Ovarian cancer growth and metabolism largely depend on changes in the signal processing of the cAMP-PKA-CREB axis, often associated with neoplastic transformation, metastasis, proliferation, and inhibition of apoptosis. In addition, the intracellular level of cAMP also determines the course of other pathways including AKT, ERK, MAPK, and mTOR, that are hypo- or hyperactivated among patients with ovarian neoplasm. With this review, we summarize the current findings on cAMP signaling in the ovary and its association with carcinogenesis, multiplication, metastasis, and survival of cancer cells. Additionally, we indicate that targeting particular stages of cAMP-dependent processes might provide promising therapeutic opportunities for the effective management of patients with ovarian cancer.

摘要

cAMP 依赖性途径是健康和肿瘤性卵巢细胞中最重要的信号级联途径之一。通过其主要效应蛋白-PKA 和 EPAC-作用,它调节基因表达和许多细胞功能。PKA 促进 cAMP 反应元件结合蛋白 (CREB) 的磷酸化,从而介导基因转录、细胞迁移、线粒体动态平衡、细胞增殖和死亡。另一方面,EPAC 参与细胞黏附、结合、分化以及细胞连接之间的相互作用。卵巢癌细胞的生长和代谢在很大程度上取决于 cAMP-PKA-CREB 轴信号处理的变化,这通常与肿瘤转化、转移、增殖和凋亡抑制有关。此外,cAMP 的细胞内水平还决定了其他途径的进程,包括 AKT、ERK、MAPK 和 mTOR,在卵巢肿瘤患者中这些途径被低激活或高激活。通过这篇综述,我们总结了 cAMP 信号在卵巢中的最新发现及其与致癌作用、增殖、转移和癌细胞存活的关联。此外,我们还指出,针对 cAMP 依赖性过程的特定阶段可能为有效管理卵巢癌患者提供有前途的治疗机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/345a/9738761/65cab5c7256b/cells-11-03835-g001.jpg

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