Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
Department of Biotechnology, University of Kerala, Thiruvananthapuram, Kerala, India.
Front Immunol. 2023 Feb 15;14:1114582. doi: 10.3389/fimmu.2023.1114582. eCollection 2023.
Adenosine monophosphate-activated protein kinase (AMPK) is a key metabolic sensor that is pivotal for the maintenance of cellular energy homeostasis. AMPK contributes to diverse metabolic and physiological effects besides its fundamental role in glucose and lipid metabolism. Aberrancy in AMPK signaling is one of the determining factors which lead to the development of chronic diseases such as obesity, inflammation, diabetes, and cancer. The activation of AMPK and its downstream signaling cascades orchestrate dynamic changes in the tumor cellular bioenergetics. It is well documented that AMPK possesses a suppressor role in the context of tumor development and progression by modulating the inflammatory and metabolic pathways. In addition, AMPK plays a central role in potentiating the phenotypic and functional reprogramming of various classes of immune cells which reside in the tumor microenvironment (TME). Furthermore, AMPK-mediated inflammatory responses facilitate the recruitment of certain types of immune cells to the TME, which impedes the development, progression, and metastasis of cancer. Thus, AMPK appears to play an important role in the regulation of anti-tumor immune response by regulating the metabolic plasticity of various immune cells. AMPK effectuates the metabolic modulation of anti-tumor immunity nutrient regulation in the TME and by virtue of its molecular crosstalk with major immune checkpoints. Several studies including that from our lab emphasize on the role of AMPK in regulating the anticancer effects of several phytochemicals, which are potential anticancer drug candidates. The scope of this review encompasses the significance of the AMPK signaling in cancer metabolism and its influence on the key drivers of immune responses within the TME, with a special emphasis on the potential use of phytochemicals to target AMPK and combat cancer by modulating the tumor metabolism.
腺苷酸活化蛋白激酶 (AMPK) 是一种关键的代谢传感器，对于维持细胞能量平衡至关重要。除了在葡萄糖和脂质代谢中的基本作用外，AMPK 还对多种代谢和生理效应有贡献。AMPK 信号的异常是导致慢性疾病（如肥胖症、炎症、糖尿病和癌症）发展的决定因素之一。AMPK 的激活及其下游信号级联反应协调了肿瘤细胞生物能量的动态变化。有充分的文献记载表明，AMPK 通过调节炎症和代谢途径，在肿瘤发生和发展过程中具有抑制作用。此外，AMPK 在增强各种免疫细胞在肿瘤微环境（TME）中的表型和功能重编程方面发挥着核心作用。此外，AMPK 介导的炎症反应有助于某些类型的免疫细胞向 TME 的募集，从而阻碍癌症的发展、进展和转移。因此，AMPK 似乎通过调节各种免疫细胞的代谢可塑性来调节抗肿瘤免疫反应中发挥重要作用。AMPK 通过调节 TME 中的抗肿瘤免疫营养素调节和与主要免疫检查点的分子串扰来实现对抗肿瘤免疫的代谢调节。包括我们实验室在内的几项研究强调了 AMPK 在调节几种植物化学物质的抗癌作用中的作用，这些植物化学物质是潜在的抗癌药物候选物。本综述的范围包括 AMPK 信号在癌症代谢中的重要性及其对 TME 中免疫反应关键驱动因素的影响，特别强调了利用植物化学物质靶向 AMPK 并通过调节肿瘤代谢来对抗癌症的潜力。
