ArticleHepatology (Baltimore, Md.)2020
Reciprocal Regulation Between Forkhead Box M1/NF-κB and Methionine Adenosyltransferase 1A Drives Liver Cancer.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- FOXM1-associated melanoma stratification: integrated multi-omics and experimental validation reveal prognostic significance and therapeutic potential.BMC cancer · 2026Article
- Amino acid metabolic reprogramming: future prospects for cholangiocarcinoma therapy.Cell death discovery · 2026Review
- The oncogenic role of FOXM1 in hepatocellular carcinoma: molecular mechanisms, clinical significance, and therapeutic potentials.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- FOXM1 upregulation, promotes immune escape in gastric cancer through activation of Notch signaling pathway.Molecular and cellular biochemistry · 2025Article
- [Ferroptosis inducer Erastin inhibits proliferation of liver cancer cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- MAT1A activation of glycolysis to promote NSCLC progression depends on stabilizing CCND1.Cell death & disease · 2024Article
- The role of forkhead box M1-methionine adenosyltransferase 2 A/2B axis in liver inflammation and fibrosis.Nature communications · 2024Article
- Hepatic prohibitin 1 and methionine adenosyltransferase α1 defend against primary and secondary liver cancer metastasis.Journal of hepatology · 2024Article
- The Interplay Between HIF-1α and EZH2 in Lung Cancer and Dual-Targeted Drug Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Signaling pathways that activate hepatic stellate cells during liver fibrosis.Frontiers in medicine · 2024Review
- Role of transcription factor FOXM1 in diabetes and its complications (Review).International journal of molecular medicine · 2023Article
- Nuclear receptor modulators inhibit osteosarcoma cell proliferation and tumour growth by regulating the mTOR signaling pathway.Cell death & disease · 2023Article
- PCLassoLog: A protein complex-based, group Lasso-logistic model for cancer classification and risk protein complex discovery.Computational and structural biotechnology journal · 2023Article
- Genetic Predisposition to Hepatocellular Carcinoma.Metabolites · 2022Review
- MELK predicts poor prognosis and promotes metastasis in esophageal squamous cell carcinoma via activating the NF‑κB pathway.International journal of oncology · 2022Article
- Forkhead Domain Inhibitor-6 Suppresses Corneal Neovascularization and Subsequent Fibrosis After Alkali Burn in Rats.Investigative ophthalmology & visual science · 2022Article
- Regulatory Networks, Management Approaches, and Emerging Treatments of Nonalcoholic Fatty Liver Disease.Canadian journal of gastroenterology & hepatology · 2022Review
- Comprehensive analysis for cellular senescence-related immunogenic characteristics and immunotherapy prediction of acute myeloid leukemia.Frontiers in pharmacology · 2022Article
- Regulatory network and interplay of hepatokines, stellakines, myokines and adipokines in nonalcoholic fatty liver diseases and nonalcoholic steatohepatitis.Frontiers in endocrinology · 2022Review
- Programming to S1PR1Circulation research · 2021Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
aimsForkhead box M1 (FOXM1) and nuclear factor kappa B (NF-ĸB) are oncogenic drivers in liver cancer that positively regulate each other. We showed that methionine adenosyltransferase 1A (MAT1A) is a tumor suppressor in the liver and inhibits NF-ĸB activity. Here, we examined the interplay between FOXM1/NF-κB and MAT1A in liver cancer. APPROACH AND
resultsWe examined gene and protein expression, effects on promoter activities and binding of proteins to promoter regions, as well as effects of FOXM1 inhibitors T0901317 (T0) and forkhead domain inhibitory-6 (FDI-6) in vitro and in xenograft and syngeneic models of liver cancer. We found, in both hepatocellular carcinoma and cholangiocarcinoma, that an induction in FOXM1 and NF-κB expression is accompanied by a fall in MATα1 (protein encoded by MAT1A). The Cancer Genome Atlas data set confirmed the inverse correlation between FOXM1 and MAT1A. Interestingly, FOXM1 directly interacts with MATα1 and they negatively regulate each other. In contrast, FOXM1 positively regulates p50 and p65 expression through MATα1, given that the effect is lost in its absence. FOXM1, MATα1, and NF-κB all bind to the FOX binding sites in the FOXM1 and MAT1A promoters. However, binding of FOXM1 and NF-κB repressed MAT1A promoter activity, but activated the FOXM1 promoter. In contrast, binding of MATα1 repressed the FOXM1 promoter. MATα1 also binds and represses the NF-κB element in the presence of p65 or p50. Inhibiting FOXM1 with either T0 or FDI-6 inhibited liver cancer cell growth in vitro and in vivo. However, inhibiting FOXM1 had minimal effects in liver cancer cells that do not express MAT1A.
conclusionsWe have found a crosstalk between FOXM1/NF-κB and MAT1A. Up-regulation in FOXM1 lowers MAT1A, but raises NF-κB, expression, and this is a feed-forward loop that enhances tumorigenesis.
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Registered trials
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