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.

The best treatment for end-stage renal disease is renal transplantation. However, it is often difficult to maintain a renal allograft healthy for a long time following transplantation. Interstitial fibrosis and tubular atrophy (IF/TA) are significant histopathologic characteristics of a compromised renal allograft. There is no effective therapy to improve renal allograft function once IF/TA sets in. Although there are many underlying factors that can induce IF/TA, the pathogenesis of IF/TA has not been fully elucidated. It has been found that epithelial-mesenchymal transition (EMT) significantly contributes to the development of IF/TA. Oxidative stress is one of the main causes that induce EMT in renal allografts. In this study, we have used H2O2 to induce oxidative stress in renal tubular epithelial cells (NRK-52e) of rats. We also pretreated NRK-52e cells with an antioxidant (N-acetyl L-cysteine (NAC)) 1 h prior to the treatment with H2O2. Furthermore, we used fenofibrate (a peroxisome proliferator-activated receptor α agonist) to treat NRK-52e cells and a renal transplant rat model. Our results reveal that oxidative stress induces EMT in NRK-52e cells, and pretreatment with NAC can suppress EMT in these cells. Moreover, fenofibrate suppresses fibrosis by ameliorating oxidative stress-induced EMT in a rat model. Thus, fenofibrate may effectively prevent the development of fibrosis in renal allograft and improve the outcome.

Glucose-6-phosphate dehydrogenase (G6PD) is the only rate-limiting enzyme in the pentose phosphate pathway (PPP). Rapidly proliferating cells require metabolites from PPP to synthesize ribonucleotides and maintain intracellular redox homeostasis. G6PD expression can be abnormally elevated in a variety of cancers. In addition, G6PD may act as a regulator of viral replication and vascular smooth muscle function. Therefore, G6PD-mediated activation of PPP may promote tumor and non-neoplastic disease progression. Recently, studies have identified post-translational modifications (PTMs) as an important mechanism for regulating G6PD function. Here, we provide a comprehensive review of various PTMs (e.g., phosphorylation, acetylation, glycosylation, ubiquitination, and glutarylation), which are identified in the regulation of G6PD structure, expression and enzymatic activity. In addition, we review signaling pathways that regulate G6PD and evaluate the role of oncogenic signals that lead to the reprogramming of PPP in tumor and non-neoplastic diseases as well as summarize the inhibitors that target G6PD.

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The somatic mutation of liver kinase B1 (LKB1) has been implicated in various tumors, which is reflected in the survival, proliferation, and metastasis of tumor cells. However, the regulation of LKB1 in lipid metabolism, a process that is involved in tumor progression is not completely clear. We conclude that LKB1 deficiency results in abnormal expression and activation of multiple molecules related to lipid metabolism which locate downstream of AMP-activated protein kinase (AMPK) or salt-induced kinase (SIK). Abnormal lipid metabolism induced by LKB1 deficiency contributes to the proliferation and metastasis of tumor cells through energy regulation.