Penugurti Vasudevarao, Manne Rajesh Kumar, Bai Ling, Kant Rajni, Lin Hui-Kuan
Department of Pathology, School of Medicine, Duke University, Durham, NC 27710, United States.
Department of Pathology, School of Medicine, Duke University, Durham, NC 27710, United States.
Semin Cancer Biol. 2024 Nov;106-107:15-27. doi: 10.1016/j.semcancer.2024.08.002. Epub 2024 Aug 26.
AMP-activated protein kinase (AMPK) is a protein kinase that plays versatile roles in response to a variety of physiological stresses, including glucose deprivation, hypoxia, and ischemia. As a kinase with pleiotropic functions, it plays a complex role in tumor progression, exhibiting both tumor-promoting and tumor-suppressing activities. On one hand, AMPK enhances cancer cell proliferation and survival, promotes cancer metastasis, and impairs anti-tumor immunity. On the other hand, AMPK inhibits cancer cell growth and survival and stimulates immune responses in a context-dependent manner. Apart from these functions, AMPK plays a key role in orchestrating aging and aging-related disorders, including cardiovascular diseases (CVD), Osteoarthritis (OA), and Diabetes. In this review article, we summarized the functions of AMPK pathway based on its oncogenic and tumor-suppressive roles and highlighted the importance of AMPK pathway in regulating cellular aging. We also spotlighted the significant role of various signaling pathways, activators, and inhibitors of AMPK in serving as therapeutic strategies for anti-cancer and anti-aging therapy.
AMP激活的蛋白激酶（AMPK）是一种蛋白激酶，在应对多种生理应激时发挥多种作用，包括葡萄糖剥夺、缺氧和缺血。作为一种具有多效性功能的激酶，它在肿瘤进展中发挥着复杂的作用，表现出促肿瘤和抑肿瘤活性。一方面，AMPK增强癌细胞增殖和存活，促进癌症转移，并损害抗肿瘤免疫。另一方面，AMPK以依赖于环境的方式抑制癌细胞生长和存活，并刺激免疫反应。除了这些功能外，AMPK在协调衰老和衰老相关疾病（包括心血管疾病（CVD）、骨关节炎（OA）和糖尿病）中起关键作用。在这篇综述文章中，我们基于AMPK的致癌和抑癌作用总结了其途径的功能，并强调了AMPK途径在调节细胞衰老中的重要性。我们还突出了AMPK的各种信号通路、激活剂和抑制剂在作为抗癌和抗衰老治疗策略方面的重要作用。
