Department of Biology, American University of Beirut, P.O. Box 11-0236 Beirut, Lebanon.
Department of Pharmacology and Therapeutics, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236 Beirut, Lebanon.
Int J Mol Sci. 2020 Sep 5;21(18):6489. doi: 10.3390/ijms21186489.
Cancer continues to be a prime contributor to global mortality. Despite tremendous research efforts and major advances in cancer therapy, much remains to be learned about the underlying molecular mechanisms of this debilitating disease. A better understanding of the key signaling events driving the malignant phenotype of cancer cells may help identify new pharmaco-targets. Cyclic adenosine 3',5'-monophosphate (cAMP) modulates a plethora of biological processes, including those that are characteristic of malignant cells. Over the years, most cAMP-mediated actions were attributed to the activity of its effector protein kinase A (PKA). However, studies have revealed an important role for the exchange protein activated by cAMP (Epac) as another effector mediating the actions of cAMP. In cancer, Epac appears to have a dual role in regulating cellular processes that are essential for carcinogenesis. In addition, the development of Epac modulators offered new routes to further explore the role of this cAMP effector and its downstream pathways in cancer. In this review, the potentials of Epac as an attractive target in the fight against cancer are depicted. Additionally, the role of Epac in cancer progression, namely its effect on cancer cell proliferation, migration/metastasis, and apoptosis, with the possible interaction of reactive oxygen species (ROS) in these phenomena, is discussed with emphasis on the underlying mechanisms and pathways.
癌症仍然是全球死亡的主要原因。尽管在癌症治疗方面进行了大量的研究和重大进展，但对于这种使人衰弱的疾病的潜在分子机制仍有许多需要了解。更好地了解驱动癌细胞恶性表型的关键信号事件可能有助于确定新的药物靶标。环腺苷酸 3'，5'-单磷酸（cAMP）调节着大量的生物学过程，包括那些与恶性细胞特征相关的过程。多年来，大多数 cAMP 介导的作用归因于其效应蛋白激酶 A（PKA）的活性。然而，研究表明，cAMP 激活的交换蛋白（Epac）作为另一种介导 cAMP 作用的效应物，起着重要的作用。在癌症中，Epac 似乎在调节致癌过程中必需的细胞过程中具有双重作用。此外，Epac 调节剂的开发为进一步探索这种 cAMP 效应物及其下游途径在癌症中的作用提供了新的途径。在这篇综述中，描绘了 Epac 作为抗癌斗争中一个有吸引力的靶点的潜力。此外，讨论了 Epac 在癌症进展中的作用，即其对癌细胞增殖、迁移/转移和凋亡的影响，以及在这些现象中活性氧（ROS）的可能相互作用，重点讨论了潜在的机制和途径。
