ArticleHepatology (Baltimore, Md.)2010
Activation of LKB1-Akt pathway independent of phosphoinositide 3-kinase plays a critical role in the proliferation of hepatocellular carcinoma from nonalcoholic steatohepatitis.
Article in Hepatology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
- Article
- Deciphering the roles of neddylation modification in hepatocellular carcinoma: Molecular mechanisms and targeted therapeutics.Genes & diseases · 2025Review
- Fructose-induced progression of steatohepatitis involves disrupting aldolase B-AMPK signaling in methionine adenosyltransferase 1A deficient mice.Metabolism: clinical and experimental · 2025Article
- Review
- S-Adenosylmethionine Negatively Regulates the Mitochondrial Respiratory Chain Repressor MCJ in the Liver.International journal of biological sciences · 2024Article
- Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency.iScience · 2023Article
- Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders.International journal of molecular sciences · 2023Review
- Genetic Predisposition to Hepatocellular Carcinoma.Metabolites · 2022Review
- Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors.Cancers · 2022Review
- Article
- Review
- Genetics, Immunity and Nutrition Boost the Switching from NASH to HCC.Biomedicines · 2021Review
- [Research progress of neural precursor cells-expressed developmentally down-regulated protein-8 in liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Article
- HuR Protein in Hepatocellular Carcinoma: Implications in Development, Prognosis and Treatment.Biomedicines · 2021Review
- Reciprocal Regulation Between Forkhead Box M1/NF-κB and Methionine Adenosyltransferase 1A Drives Liver Cancer.Hepatology (Baltimore, Md.) · 2020Article
- mRNA Post-Transcriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer.International journal of molecular sciences · 2020Review
- PINE: An Automation Tool to Extract and Visualize Protein-Centric Functional Networks.Journal of the American Society for Mass Spectrometry · 2020Article
- The malignancy of liver cancer cells is increased by IL-4/ERK/AKT signaling axis activity triggered by irradiated endothelial cells.Journal of radiation research · 2020Article
- The role of MDM2-p53 axis dysfunction in the hepatocellular carcinoma transformation.Cell death discovery · 2020Review
- Methionine adenosyltransferases in liver cancer.World journal of gastroenterology · 2019Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
unlabelledLKB1, originally considered a tumor suppressor, plays an important role in hepatocyte proliferation and liver regeneration. Mice lacking the methionine adenosyltransferase (MAT) gene MAT1A exhibit a chronic reduction in hepatic S-adenosylmethionine (SAMe) levels, basal activation of LKB1, and spontaneous development of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). These results are relevant for human health because patients with liver cirrhosis, who are at risk to develop HCC, have a marked reduction in hepatic MAT1A expression and SAMe synthesis. In this study, we isolated a cell line (SAMe-deficient [SAMe-D]) from MAT1A knockout (MAT1A-KO) mouse HCC to examine the role of LKB1 in the development of liver tumors derived from metabolic disorders. We found that LKB1 is required for cell survival in SAMe-D cells. LKB1 regulates Akt-mediated survival independent of phosphoinositide 3-kinase, adenosine monophosphate protein-activated kinase (AMPK), and mammalian target of rapamycin complex (mTORC2). In addition, LKB1 controls the apoptotic response through phosphorylation and retention of p53 in the cytoplasm and the regulation of herpesvirus-associated ubiquitin-specific protease (HAUSP) and Hu antigen R (HuR) nucleocytoplasmic shuttling. We identified HAUSP as a target of HuR. Finally, we observed cytoplasmic staining of p53 and p-LKB1(Ser428) in a NASH-HCC animal model (from MAT1A-KO mice) and in liver biopsies obtained from human HCC derived from both alcoholic steatohepatitis and NASH.
conclusionThe SAMe-D cell line is a relevant model of HCC derived from NASH disease in which LKB1 is the principal conductor of a new regulatory mechanism and could be a practical tool for uncovering new therapeutic strategies.
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