ArticleMatrix biology : journal of the International Society for Matrix Biology2017
The perlecan-interacting growth factor progranulin regulates ubiquitination, sorting, and lysosomal degradation of sortilin.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Tumor-derived progranulin promotes macrophage cholesterol efflux and associated immunosuppressive features in oral squamous cell carcinoma.Journal of translational medicine · 2026Article
- IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis.Experimental & molecular medicine · 2023Article
- Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression.Scientific reports · 2023Article
- Progranulin and EGFR modulate receptor-like tyrosine kinase sorting and stability in mesothelioma cells.American journal of physiology. Cell physiology · 2023Article
- Heparan sulfate proteoglycan in Alzheimer's disease: aberrant expression and functions in molecular pathways related to amyloid-β metabolism.American journal of physiology. Cell physiology · 2023Review
- Progranulin Oncogenic Network in Solid Tumors.Cancers · 2023Review
- Complexity of progranulin mechanisms of action in mesothelioma.Journal of experimental & clinical cancer research : CR · 2022Article
- Deciphering Mechanisms of Action of Sortilin/Neurotensin Receptor-3 in the Proliferation Regulation of Colorectal and Other Cancers.International journal of molecular sciences · 2022Review
- Combined miR-486 and GP88 (Progranulin) Serum Levels Are Suggested as Supportive Biomarkers for Therapy Decision in Elderly Prostate Cancer Patients.Life (Basel, Switzerland) · 2022Article
- SorCS3 promotes the internalization of p75Cell death & disease · 2022Article
- A functional outside-in signaling network of proteoglycans and matrix molecules regulating autophagy.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Angiostatic cues from the matrix: Endothelial cell autophagy meets hyaluronan biology.The Journal of biological chemistry · 2020Review
- Progranulin/EphA2 axis: A novel oncogenic mechanism in bladder cancer.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Genetic Regulation of Neuronal Progranulin Reveals a Critical Role for the Autophagy-Lysosome Pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Matrix modeling and remodeling: A biological interplay regulating tissue homeostasis and diseases.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Sortilin inhibition limits secretion-induced progranulin-dependent breast cancer progression and cancer stem cell expansion.Breast cancer research : BCR · 2018Article
- Extracellular matrix: The driving force of mammalian diseases.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- Endorepellin remodels the endothelial transcriptome toward a pro-autophagic and pro-mitophagic gene signature.The Journal of biological chemistry · 2018Article
- Progranulin: Functions and neurologic correlations.Neurology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Despite extensive clinical and experimental studies over the past decades, the pathogenesis and progression to the castration-resistant stage of prostate cancer remains largely unknown. Progranulin, a secreted growth factor, strongly binds the heparin-sulfate proteoglycan perlecan, and counteracts its biological activity. We established that progranulin acts as an autocrine growth factor and promotes prostate cancer cell motility, invasion, and anchorage-independent growth. Progranulin was overexpressed in prostate cancer tissues vis-à-vis non-neoplastic tissues supporting the hypothesis that progranulin may play a key role in prostate cancer progression. However, progranulin's mode of action is not well understood and proteins regulating progranulin signaling have not been identified. Sortilin, a single-pass type I transmembrane protein of the Vps10 family, binds progranulin in neurons and targets progranulin for lysosomal degradation. Significantly, in DU145 and PC3 cells, we detected very low levels of sortilin associated with high levels of progranulin production and enhanced motility. Restoring sortilin expression decreased progranulin levels, inhibited motility and anchorage-independent growth and destabilized Akt. These results demonstrated a critical role for sortilin in regulating progranulin and suggest that sortilin loss may contribute to prostate cancer progression. Here, we provide the novel observation that progranulin downregulated sortilin protein levels independent of transcription. Progranulin induced sortilin ubiquitination, internalization via clathrin-dependent endocytosis and sorting into early endosomes for lysosomal degradation. Collectively, these results constitute a regulatory feed-back mechanism whereby sortilin downregulation ensures sustained progranulin-mediated oncogenesis.
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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.