ArticleBreast cancer research : BCR2018
Sortilin inhibition limits secretion-induced progranulin-dependent breast cancer progression and cancer stem cell expansion.
Article in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 73 citations in OpenAlex.
- Spatial Autocorrelation Aware Resampling Improves Cell-Cell Interaction Inference in Spatial Transcriptomics Data.bioRxiv : the preprint server for biology · 2026Article
- Tumor-derived progranulin promotes macrophage cholesterol efflux and associated immunosuppressive features in oral squamous cell carcinoma.Journal of translational medicine · 2026Article
- Targeting fibroblast TXNDC5 resolves tumor desmoplasia and PD-1 resistance in colorectal cancer with mesenchymal traits.Nature communications · 2026Article
- Spatially resolved single-cell analyses of human meningioma identify novel cell states influencing tumor microenvironment and progression.Nature genetics · 2026Article
- Dysregulation of adipokines in the serum of breast cancer patients - role in pathogenesis and potential clinical application (preliminary studies).Frontiers in immunology · 2026Article
- Analysing the effect of full-length and C-terminally truncated progranulin on proliferation, colony formation, and migration in HepG2 and U87 cells.Scientific reports · 2025Article
- Single-Cell Sequencing Reveals Novel Tumor Populations and Their Interplay with the Immune Microenvironment in a Pleomorphic Rhabdomyosarcoma.International journal of molecular sciences · 2025Article
- Article
- Sortilin-1, Targeted by miR-146a, Regulates the Behavior of Non-Small Cell Lung Cancer.Thoracic cancer · 2025Article
- SORT1 promote the metastasis and invasion of hepatocellular carcinoma via p38/β-catenin/ZEB1 signaling pathway.Cell death & disease · 2025Article
- Ribonuclease 1 Induces T-Cell Dysfunction and Impairs CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Isobaric Tagging and Data Independent Acquisition as Complementary Strategies for Proteome Profiling on an Orbitrap Astral Mass Spectrometer.Journal of proteome research · 2025Article
- Isobaric Tagging and Data Independent Acquisition as Complementary Strategies for Proteome Profiling on an Orbitrap Astral Mass Spectrometer.bioRxiv : the preprint server for biology · 2024Article
- Sortilin-mediated translocation of mitochondrial ACSL1 impairs adipocyte thermogenesis and energy expenditure in male mice.Nature communications · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Novel Transcriptional and DNA Methylation Abnormalities of SORT1 Gene in Non-Small Cell Lung Cancer.Cancers · 2024Article
- Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment.Cancer research communications · 2024Article
- An anti-sortilin affibody-peptide fusion inhibits sortilin-mediated progranulin degradation.Frontiers in immunology · 2024Article
- Interleukin-6 Induces Stem Cell Propagation through Liaison with the Sortilin-Progranulin Axis in Breast Cancer.Cancers · 2023Article
- Progranulin promoted the proliferation, metastasis, and suppressed apoptosis via JAK2-STAT3/4 signaling pathway in papillary thyroid carcinoma.Cancer cell international · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer progression is influenced by genetic aberrations in the cancer cell population as well as by other factors including the microenvironment present within a tumour. Direct interactions between various cell types as well as cellular signalling via secreted cytokines can drive key tumourigenic properties associated with disease progression and treatment resistance. Also, cancer stem cell functions are influenced by the microenvironment. This challenging subset of cells has been linked to malignant properties. Within a screen, using in vivo like growth conditions, we identified progranulin as a highly secreted cytokine affecting cancer stem cells in breast cancer. This cytokine is known to play a role in numerous biological and tumour-related processes including therapy resistance in a range of cancer types.
methodsDifferent in vitro and in vivo relevant conditions were used to validate breast cancer stem cell expansion mediated by progranulin and its receptor sortilin. Small interfering ribonucleic acid (siRNA) and pharmacological inhibition of sortilin were used to elucidate the role of sortilin as a functional receptor during progranulin-induced breast cancer stem cell propagation, both in vitro and in vivo, using breast cancer xenograft models. In addition, single-cell gene expression profiling as well as a Sox2 reporter breast cancer cell line were used to validate the role of dedifferentiation mediated by progranulin.
resultsIn various in vivo-like screening assays, progranulin was identified as a potent cancer stem cell activator, highly secreted in ERα-negative breast cancer as well as in ERα-positive breast cancer under hypoxic adaptation. Progranulin exposure caused dedifferentiation as well as increased proliferation of the cancer stem cell pool, a process that was shown to be dependent on its receptor sortilin. Subcutaneous injections of progranulin or its active domain (GRN A) induced lung metastases in breast cancer xenograft models, supporting a major role for progranulin in cancer progression. Importantly, an orally bioavailable small molecule (AF38469) targeting sortilin, blocked GRN A-induced lung metastases and prevented cancer cell infiltration of the skin.
conclusionThe collective results suggest that sortilin targeting represents a potential novel breast cancer therapy approach inhibiting tumour progression driven by secretion and microenvironmental influences.
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