ArticleJournal of hepatology2012
M6P/IGF2R modulates the invasiveness of liver cells via its capacity to bind mannose 6-phosphate residues.
Article in Journal of hepatology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.Aging and disease · 2025Review
- Peptide-Based siRNA Nanocomplexes Targeting Hepatic Stellate Cells.Biomolecules · 2023Article
- Comparative site-specific N-glycoproteome analysis reveals aberrant N-glycosylation and gives insights into mannose-6-phosphate pathway in cancer.Communications biology · 2023Article
- Lysosomes, curcumin, and anti-tumor effects: how are they linked?Frontiers in pharmacology · 2023Review
- Impaired Retrograde Transport Due to Lack of TBC1D5 Contributes to the Trafficking Defect of Lysosomal Cathepsins in Ischemic/Hypoxic Cardiomyocytes.Frontiers in cardiovascular medicine · 2021Article
- Review
- Targeted Drug Delivery to Hepatic Stellate Cells for the Treatment of Liver Fibrosis.The Journal of pharmacology and experimental therapeutics · 2019Review
- Maternal transmission of an Igf2r domain 11: IGF2 binding mutant allele (Igf2rScientific reports · 2019Article
- HIV Infection Induces Extracellular Cathepsin B Uptake and Damage to Neurons.Scientific reports · 2019Article
- Mannose and Mannose-6-Phosphate Receptor-Targeted Drug Delivery Systems and Their Application in Cancer Therapy.Advanced healthcare materials · 2018Review
- Alcohol and hepatitis virus-dysregulated lncRNAs as potential biomarkers for hepatocellular carcinoma.Oncotarget · 2018Article
- Preparation and characterization of the Adriamycin-loaded amphiphilic chitosan nanoparticles and their application in the treatment of liver cancer.Oncology letters · 2017Article
- microRNA-802/Rnd3 pathway imposes on carcinogenesis and metastasis of fine particulate matter exposure.Oncotarget · 2016Article
- Long noncoding RNA GAS5 suppresses the migration and invasion of hepatocellular carcinoma cells via miR-21.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- The mannose 6-phosphate-binding sites of M6P/IGF2R determine its capacity to suppress matrix invasion by squamous cell carcinoma cells.The Biochemical journal · 2013Article
- Recombinant human acid sphingomyelinase as an adjuvant to sorafenib treatment of experimental liver cancer.PloS one · 2013Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R), a multifunctional protein, plays a central role in intracellular targeting of lysosomal enzymes and control of insulin-like growth factor II (IGF-II) bioactivity. Importantly, the gene encoding this receptor is frequently inactivated in a wide range of malignant tumors including hepatocellular carcinomas. Thus, M6P/IGF2R is considered a putative liver tumor suppressor. The aim of this study was to establish the impact of the receptor on the invasive properties of liver cells.
methodsReconstitution experiments were performed by expression of wild type and mutant M6P/IGF2R in receptor-deficient FRL14 fetal rat liver cells. RNA interference was used to induce M6P/IGF2R downregulation in receptor-positive MIM-1-4 mouse hepatocytes.
resultsWe show that the M6P/IGF2R status exerts a strong impact on the invasiveness of tumorigenic rodent liver cells. M6P/IGF2R-deficient fetal rat liver cells hypersecrete lysosomal cathepsins and penetrate extracellular matrix barriers in a cathepsin-dependent manner. Forced expression of M6P/IGF2R restores intracellular transport of cathepsins to lysosomes and concomitantly reduces the tumorigenicity and invasive potential of these cells. Conversely, M6P/IGF2R knock-down in receptor-positive mouse hepatocytes causes increased cathepsin secretion as well as enhanced cell motility and invasiveness. We also demonstrate that functional M6P-binding sites are important for the anti-invasive properties of M6P/IGF2R, whereas the capacity to bind IGF-II is dispensable for the anti-invasive activity of the receptor in liver cells.
conclusionsM6P/IGF2R restricts liver cell invasion by preventing the pericellular action of M6P-modified proteins.
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Registered trials
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.