ArticleOncogene2015
Progranulin promotes Temozolomide resistance of glioblastoma by orchestrating DNA repair and tumor stemness.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
- Progranulin promotes glioma progression via interaction with cathepsin D and serves as a diagnostic and prognostic biomarker.Discover oncology · 2026Article
- Article
- Progranulin promotes glioma progression through the M2-TGF-β axis: targeted therapy with SORT1-loaded HAMA hydrogel microspheres.American journal of translational research · 2026Article
- Targeting asymmetric division in cancer stem cells: implications for relapse and resistance.Cancer cell international · 2025Review
- 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
- Cut the fat: targeting cholesterol and lipid metabolism in glioblastoma.Cell death & disease · 2025Review
- Glioblastoma at the crossroads: current understanding and future therapeutic horizons.Signal transduction and targeted therapy · 2025Review
- Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence.bioRxiv : the preprint server for biology · 2025Article
- The role of progranulin in macrophages of a glioblastoma model.Journal of neuro-oncology · 2024Article
- The pathogenic germline ETV4 P433L mutation identified in multiple primary lung cancer affect tumor stem-like property by Wnt/β-catenin pathway.Cell death & disease · 2024Article
- Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.Cytokine & growth factor reviews · 2024Review
- PGRN inhibits CD8Cancer immunology, immunotherapy : CII · 2024Article
- Glioblastoma biomarkers in urinary extracellular vesicles reveal the potential for a 'liquid gold' biopsy.British journal of cancer · 2024Article
- Review
- Gene expression analysis suggests immunosuppressive roles of endolysosomes in glioblastoma.PloS one · 2024Article
- LINC00963-FOSB-mediated transcription activation of UBE3C enhances radioresistance of breast cancer cells by inducing ubiquitination-dependent protein degradation of TP73.Journal of translational medicine · 2023Article
- Progranulin Oncogenic Network in Solid Tumors.Cancers · 2023Review
- Progranulin modulates the progression of non-small cell lung cancer through lncRNA H19.American journal of translational research · 2023Article
- Polyadenosine diphosphate-ribose polymerase inhibitors: advances, implications, and challenges in tumor radiotherapy sensitization.Frontiers in oncology · 2023Review
- Preclinical Interventions in Mouse Models of Frontotemporal Dementia Due to Progranulin Mutations.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults with a dismal prognosis. Current therapy of surgical removal combined with Temozolomide (TMZ) and radiation therapy only slightly prolongs the survival of GBM patients. Thus, it is essential to elucidate mechanism underlying its highly malignant properties in order to develop efficacious therapeutic regimens. In this study, we showed that progranulin (PGRN) was overexpressed in most GBM cell lines and the majority of human tumor samples. PGRN overexpression conferred GBM cells with tumorigenic properties and TMZ resistance by upregulating DNA repair (PARP, ATM, BRCA1, Rad51, XRCC1 and so on) and cancer stemness (CD133, CD44, ABCG2) genes, in part via an AP-1 transcription factor, specifically cFos/JunB. Curcumin, an AP-1 inhibitor, was also found to regulate PGRN promoter activity and expression including its downstream effectors aforementioned. These data suggested a feedforward loop between PGRN signaling and AP-1. PGRN depletion significantly decreased unlimited self-renewal and multilineage differentiation and the malignant properties of GBMs cells S1R1, and enhanced their vulnerability to TMZ. In addition, S1R1 depleted of PGRN also lost the ability to form tumor in an orthotopic xenograft mouse model. In conclusion, PGRN had a critical role in the pathogenesis and chemoresistance of GBM and functioned at the top of the hierarchy of cellular machinery that modulates both DNA repair pathways and cancer stemness. Our data suggest that a new strategy combining current regimens with compounds targeting PGRN/AP-1 loop like curcumin may significantly improve the therapeutic outcome of GBM.
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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.