ArticleJournal of hepatology2024
Hepatic prohibitin 1 and methionine adenosyltransferase α1 defend against primary and secondary liver cancer metastasis.
Article in Journal of hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
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- Review
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- A novel role of secreted methionine adenosyltransferase α2 in colorectal liver metastases.Journal of experimental & clinical cancer research : CR · 2025Article
- Unveiling the role of coagulation-related genes in acute myeloid leukemia prognosis and immune microenvironment through machine learning.European journal of medical research · 2025Article
- Inflammation and Immunity in Liver Neoplasms: Implications for Future Therapeutic Strategies.Molecular cancer therapeutics · 2025Review
- A novel liquid-liquid phase separation related gene signature including ARL6IP4 predicts prognosis and immune landscape in colorectal cancer.Frontiers in immunology · 2025Article
- Targeting KAT7 inhibits the progression of colorectal cancer.Theranostics · 2025Article
- Immune dynamics shaping pre-metastatic and metastatic niches in liver metastases: from molecular mechanisms to therapeutic strategies.Molecular cancer · 2024Review
- Immunogenomic features of radiologically distinctive nodules in multiple primary lung cancer.Cancer immunology, immunotherapy : CII · 2024Article
- Two-polarized roles of transcription factor FOSB in lung cancer progression and prognosis: dependent on p53 status.Journal of experimental & clinical cancer research : CR · 2024Article
- Dysfunctional VLDL metabolism in MASLD.npj metabolic health and disease · 2024Review
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Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsThe liver is a common site of cancer metastasis, most commonly from colorectal cancer, and primary liver cancers that have metastasized are associated with poor outcomes. The underlying mechanisms by which the liver defends against these processes are largely unknown. Prohibitin 1 (PHB1) and methionine adenosyltransferase 1A (MAT1A) are highly expressed in the liver. They positively regulate each other and their deletion results in primary liver cancer. Here we investigated their roles in primary and secondary liver cancer metastasis.
methodsWe identified common target genes of PHB1 and MAT1A using a metastasis array, and measured promoter activity and transcription factor binding using luciferase reporter assays and chromatin immunoprecipitation, respectively. We examined how PHB1 or MAT1A loss promotes liver cancer metastasis and whether their loss sensitizes to colorectal liver metastasis (CRLM).
resultsMatrix metalloproteinase-7 (MMP-7) is a common target of MAT1A and PHB1 and its induction is responsible for increased migration and invasion when MAT1A or PHB1 is silenced. Mechanistically, PHB1 and MAT1A negatively regulate MMP7 promoter activity via an AP-1 site by repressing the MAFG-FOSB complex. Loss of MAT1A or PHB1 also increased MMP-7 in extracellular vesicles, which were internalized by colon and pancreatic cancer cells to enhance their oncogenicity. Low hepatic MAT1A or PHB1 expression sensitized to CRLM, but not if endogenous hepatic MMP-7 was knocked down first, which lowered CD4
conclusionWe have identified a PHB1/MAT1A-MAFG/FOSB-MMP-7 axis that controls primary liver cancer metastasis and sensitization to CRLM. IMPACT AND IMPLICATIONS: Primary and secondary liver cancer metastasis is associated with poor outcomes but whether the liver has underlying defense mechanism(s) against metastasis is unknown. Here we examined the hypothesis that hepatic prohibitin 1 (PHB1) and methionine adenosyltransferase 1A (MAT1A) cooperate to defend the liver against metastasis. Our studies found PHB1 and MAT1A form a complex that suppresses matrix metalloproteinase-7 (MMP-7) at the transcriptional level and loss of either PHB1 or MAT1A sensitizes the liver to metastasis via MMP-7 induction. Strategies that target the PHB1/MAT1A-MMP-7 axis may be a promising approach for the treatment of primary and secondary liver cancer metastasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.