Background

Live kinase B1 (LKB1) is a tumor suppressor that is mutated in Peutz-Jeghers syndrome (PJS) and a variety of cancers. Lkb1 encodes serine-threonine kinase (STK) 11 that activates AMP-activated protein kinase (AMPK) and its 13 superfamily members, regulating multiple biological processes, such as cell polarity, cell cycle arrest, embryo development, apoptosis, and bioenergetics metabolism. Increasing evidence has highlighted that deficiency of LKB1 in cancer cells induces extensive metabolic alterations that promote tumorigenesis and development. LKB1 also participates in the maintenance of phenotypes and functions of normal cells through metabolic regulation.

Scope of review

Given the important role of LKB1 in metabolic regulation, we provide an overview of the association of metabolic alterations in glycolysis, aerobic oxidation, the pentose phosphate pathway (PPP), gluconeogenesis, glutamine, lipid, and serine induced by aberrant LKB1 signals in tumor progression, non-neoplastic diseases, and functions of immune cells.

Major conclusions

In this review, we summarize layers of evidence demonstrating that disordered metabolisms in glucose, glutamine, lipid, and serine caused by LKB1 deficiency promote carcinogenesis and non-neoplastic diseases. The metabolic reprogramming resulting from the loss of LKB1 confers cancer cells with growth or survival advantages. Nevertheless, it also causes a metabolic frangibility for LKB1-deficient cancer cells. The metabolic regulation of LKB1 also plays a vital role in maintaining cellular phenotype in the progression of non-neoplastic diseases. In addition, lipid metabolic regulation of LKB1 plays an important role in controlling the function, activity, proliferation, and differentiation of several types of immune cells. We conclude that in-depth knowledge of metabolic pathways regulated by LKB1 is conducive to identifying therapeutic targets and developing drug combinations to treat cancers and metabolic diseases and achieve immunoregulation.

中文翻译：

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LKB1 缺陷诱导的肿瘤发生和非肿瘤性疾病中的代谢重编程

背景

活激酶 B1 (LKB1) 是一种肿瘤抑制因子，在 Peutz-Jeghers 综合征 (PJS) 和多种癌症中发生突变。Lkb1编码丝氨酸-苏氨酸激酶 (STK) 11，可激活 AMP 活化蛋白激酶 (AMPK) 及其 13 个超家族成员，调节多种生物过程，如细胞极性、细胞周期停滞、胚胎发育、细胞凋亡和生物能量代谢。越来越多的证据表明，癌细胞中 LKB1 的缺乏会诱导广泛的代谢改变，从而促进肿瘤的发生和发展。LKB1 还通过代谢调节参与维持正常细胞的表型和功能。

审查范围

鉴于 LKB1 在代谢调节中的重要作用，我们概述了由异常 LKB1 信号在肿瘤进展中诱导的糖酵解、有氧氧化、磷酸戊糖途径 (PPP)、糖异生、谷氨酰胺、脂质和丝氨酸中代谢改变的关联、非肿瘤性疾病和免疫细胞的功能。

主要结论

在这篇综述中，我们总结了一系列证据，证明由 LKB1 缺乏引起的葡萄糖、谷氨酰胺、脂质和丝氨酸代谢紊乱会促进致癌作用和非肿瘤性疾病。LKB1 缺失导致的代谢重编程赋予癌细胞生长或存活优势。尽管如此，它也会导致 LKB1 缺陷的癌细胞的代谢脆弱性。LKB1 的代谢调节在维持非肿瘤性疾病进展中的细胞表型方面也起着至关重要的作用。此外，LKB1 的脂质代谢调节在控制多种类型免疫细胞的功能、活性、增殖和分化方面起着重要作用。