Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
J Biol Chem. 2023 Apr;299(4):104570. doi: 10.1016/j.jbc.2023.104570. Epub 2023 Mar 3.
Liver kinase B1 (LKB1) is a serine-threonine kinase that participates in multiple cellular and biological processes, including energy metabolism, cell polarity, cell proliferation, cell migration, and many others. LKB1 is initially identified as a germline-mutated causative gene in Peutz-Jeghers syndrome and is commonly regarded as a tumor suppressor due to frequent inactivation in a variety of cancers. LKB1 directly binds and activates its downstream kinases including the AMP-activated protein kinase (AMPK) and AMPK-related kinases by phosphorylation, which has been intensively investigated for the past decades. An increasing number of studies have uncovered the posttranslational modifications (PTMs) of LKB1 and consequent changes in its localization, activity, and interaction with substrates. The alteration in LKB1 function as a consequence of genetic mutations and aberrant upstream signaling regulation leads to tumor development and progression. Here, we review current knowledge about the mechanism of LKB1 in cancer and the contributions of PTMs, such as phosphorylation, ubiquitination, SUMOylation, acetylation, prenylation, and others, to the regulation of LKB1 function, offering new insights into the therapeutic strategies in cancer.
肝激酶 B1（LKB1）是一种丝氨酸/苏氨酸激酶，参与多种细胞和生物学过程，包括能量代谢、细胞极性、细胞增殖、细胞迁移等。LKB1 最初被鉴定为 Peutz-Jeghers 综合征中的种系突变致病基因，由于在多种癌症中经常失活，通常被认为是一种肿瘤抑制因子。LKB1 通过磷酸化直接结合并激活其下游激酶，包括 AMP 激活的蛋白激酶（AMPK）和 AMPK 相关激酶，这在过去几十年中得到了深入研究。越来越多的研究揭示了 LKB1 的翻译后修饰（PTMs）及其随后在定位、活性和与底物相互作用方面的变化。由于遗传突变和异常上游信号调节导致 LKB1 功能改变，导致肿瘤的发生和发展。在这里，我们综述了目前关于 LKB1 在癌症中的作用机制以及 PTMs（如磷酸化、泛素化、SUMO 化、乙酰化、 prenylation 等）对 LKB1 功能调节的贡献，为癌症的治疗策略提供了新的见解。
