ArticleHepatology (Baltimore, Md.)2017
Prohibitin 1 suppresses liver cancer tumorigenesis in mice and human hepatocellular and cholangiocarcinoma cells.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- LINE-1 retrotransposition modulates metabolic stress and promotes cuproptosis resistance in lung squamous cell carcinoma by disrupting mitochondrial membrane homeostasis.Journal of translational medicine · 2026Article
- c-MAF Transcriptionally Activates Slc40a1 to Repress Ferroptosis in Sepsis-Associated Encephalopathy.CNS neuroscience & therapeutics · 2026Article
- Importance of SUMOylation Consensus Sequence of MAFK in Regulating EMT, Tumor Growth, Stemness, and Drug Resistance.Cancer science · 2026Article
- Prohibitins: emerging host targets of bacteria and viruses at the plasma membrane, mitochondria, and cytoplasm.Microbial cell (Graz, Austria) · 2026Article
- Methionine Adenosyltransferase 1A and S-Adenosylmethionine in Alcohol-Associated Liver Disease.Antioxidants (Basel, Switzerland) · 2025Review
- A multi-omics prognostic model of cuproptosis affects the prognosis of stomach adenocarcinoma.Clinical epigenetics · 2025Article
- Emerging roles of prohibitins in cancer: an update.Cancer gene therapy · 2025Review
- Demystifying metabolic‒immune crosstalk: how amino acid metabolic reprogramming shapes the malignant phenotype and macrophage polarization of biliary and pancreatic tumors.International journal of biological sciences · 2025Review
- Hepatic prohibitin 1 and methionine adenosyltransferase α1 defend against primary and secondary liver cancer metastasis.Journal of hepatology · 2024Article
- Beneficial Effects of Low-Grade Mitochondrial Stress on Metabolic Diseases and Aging.Yonsei medical journal · 2024Review
- Subcellular distribution of prohibitin 1 in rat liver during liver regeneration and its cellular implication.World journal of hepatology · 2024Article
- Pan-cancer Analysis Combined with Experiments Deciphers PHB Regulation for Breast Cancer Cell Survival and Predicts Biomarker Function.Combinatorial chemistry & high throughput screening · 2024Article
- Prohibitions in the meta-inflammatory response: a review.Frontiers in molecular biosciences · 2024Review
- Review
- LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1-p53/c-Myc axis.Cancer science · 2023Article
- Deletion of adipocyte prohibitin 1 exacerbates high-fat diet-induced steatosis but not liver inflammation and fibrosis.Hepatology communications · 2022Article
- The function of prohibitins in mitochondria and the clinical potentials.Cancer cell international · 2022Review
- Prohibitin 1 interacts with p53 in the regulation of mitochondrial dynamics and chemoresistance in gynecologic cancers.Journal of ovarian research · 2022Article
- Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication.Signal transduction and targeted therapy · 2020Review
- Reciprocal Regulation Between Forkhead Box M1/NF-κB and Methionine Adenosyltransferase 1A Drives Liver Cancer.Hepatology (Baltimore, Md.) · 2020Article
Corrections and comments
- Erratum issuedCorrection.2017
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Prohibitin 1 (PHB1) is best known as a mitochondrial chaperone, and its role in cancer is conflicting. Mice lacking methionine adenosyltransferase α1 (MATα1) have lower PHB1 expression, and we reported that c-MYC interacts directly with both proteins. Furthermore, c-MYC and MATα1 exert opposing effects on liver cancer growth, prompting us to examine the interplay between PHB1, MATα1, and c-MYC and PHB1's role in liver tumorigenesis. We found that PHB1 is highly expressed in normal hepatocytes and bile duct epithelial cells and down-regulated in most human hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). In HCC and CCA cells, PHB1 expression correlates inversely with growth. PHB1 and MAT1A positively regulate each other's expression, whereas PHB1 negatively regulates the expression of c-MYC, MAFG, and c-MAF. Both PHB1 and MATα1 heterodimerize with MAX, bind to the E-box element, and repress E-box promoter activity. PHB1 promoter contains a repressive E-box element and is occupied mainly by MAX, MNT, and MATα1 in nonmalignant cholangiocytes and noncancerous tissues that switched to c-MYC, c-MAF, and MAFG in cancer cells and human HCC/CCA. All 8-month-old liver-specific Phb1 knockout mice developed HCC, and one developed CCA. Five-month-old Phb1 heterozygotes, but not Phb1 flox mice, developed aberrant bile duct proliferation; and one developed CCA 3.5 months after left and median bile duct ligation. Phb1 heterozygotes had a more profound fall in the expression of glutathione synthetic enzymes and higher hepatic oxidative stress following left and median bile duct ligation.
conclusionWe have identified that PHB1, down-regulated in most human HCC and CCA, heterodimerizes with MAX to repress the E-box and positively regulates MAT1A while suppressing c-MYC, MAFG, and c-MAF expression; in mice, reduced PHB1 expression predisposes to the development of cholestasis-induced CCA. (Hepatology 2017;65:1249-1266).
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