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肝脏激酶B1(LKB1)的最新研究进展:表达、调控、下游信号传导及抑癌功能

Recent progress on liver kinase B1 (LKB1): expression, regulation, downstream signaling and cancer suppressive function.

作者信息

Gan Ren-You, Li Hua-Bin

机构信息

School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China.

Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.

出版信息

Int J Mol Sci. 2014 Sep 19;15(9):16698-718. doi: 10.3390/ijms150916698.

DOI:10.3390/ijms150916698
PMID:25244018
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4200829/
Abstract

Liver kinase B1 (LKB1), known as a serine/threonine kinase, has been identified as a critical cancer suppressor in many cancer cells. It is a master upstream kinase of 13 AMP-activated protein kinase (AMPK)-related protein kinases, and possesses versatile biological functions. LKB1 gene is mutated in many cancers, and its protein can form different protein complexes with different cellular localizations in various cell types. The expression of LKB1 can be regulated through epigenetic modification, transcriptional regulation and post-translational modification. LKB1 dowcnstream pathways mainly include AMPK, microtubule affinity regulating kinase (MARK), salt-inducible kinase (SIK), sucrose non-fermenting protein-related kinase (SNRK) and brain selective kinase (BRSK) signalings, etc. This review, therefore, mainly discusses recent studies about the expression, regulation, downstream signaling and cancer suppressive function of LKB1, which can be helpful for better understanding of this molecular and its significance in cancers.

摘要

肝脏激酶B1(LKB1),作为一种丝氨酸/苏氨酸激酶,已被确定为许多癌细胞中的关键抑癌基因。它是13种AMP激活蛋白激酶(AMPK)相关蛋白激酶的主要上游激酶,具有多种生物学功能。LKB1基因在许多癌症中发生突变,其蛋白在不同细胞类型中可形成具有不同细胞定位的不同蛋白复合物。LKB1的表达可通过表观遗传修饰、转录调控和翻译后修饰进行调节。LKB1下游通路主要包括AMPK、微管亲和力调节激酶(MARK)、盐诱导激酶(SIK)、蔗糖非发酵蛋白相关激酶(SNRK)和脑选择性激酶(BRSK)信号等。因此,本综述主要讨论了关于LKB1的表达、调控、下游信号传导和抑癌功能的最新研究,这有助于更好地理解该分子及其在癌症中的意义。

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本文引用的文献

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LKB1 and AMPK and the cancer-metabolism link - ten years after.LKB1 和 AMPK 与癌症代谢的联系——十年之后。
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Loss of LKB1 expression reduces the latency of ErbB2-mediated mammary gland tumorigenesis, promoting changes in metabolic pathways.LKB1 表达缺失会缩短 ErbB2 介导的乳腺肿瘤发生的潜伏期,促进代谢途径的改变。
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Liver kinase b1 is required for white adipose tissue growth and differentiation.
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Mitophagy bridges DNA sensing with metabolic adaption to expand lung cancer stem-like cells.线粒体自噬将 DNA 传感与代谢适应联系起来,以扩大肺癌干细胞样细胞。
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Liver Kinase B1 Functions as a Regulator for Neural Development and a Therapeutic Target for Neural Repair.肝激酶 B1 作为神经发育的调节剂和神经修复的治疗靶点。
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Liver kinase B1 rs9282860 polymorphism and risk for multiple sclerosis in White and Black Americans.肝激酶 B1(rs9282860) 多态性与白人和黑人美国人多发性硬化症的风险。
Mult Scler Relat Disord. 2021 Oct;55:103185. doi: 10.1016/j.msard.2021.103185. Epub 2021 Aug 2.
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Evaluation of LKB1 and Serine-Glycine Metabolism Pathway Genes (SHMT1 and GLDC) Expression in AML.急性髓系白血病中LKB1及丝氨酸-甘氨酸代谢途径基因(SHMT1和GLDC)表达的评估
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Altered LKB1/AMPK/TSC1/TSC2/mTOR signaling causes disruption of Sertoli cell polarity and spermatogenesis.LKB1/AMPK/TSC1/TSC2/mTOR 信号改变导致支持细胞极性和精子发生紊乱。
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