ArticleInternational journal of molecular sciences2019
ANGPTL4 Induces TMZ Resistance of Glioblastoma by Promoting Cancer Stemness Enrichment via the EGFR/AKT/4E-BP1 Cascade.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- The role of ANGPTL4 in cancer: A meta-analysis of observational studies and multi-omics investigation.PloS one · 2025Pooled it
- BCL11B predetermines a persister state in breast cancer that is reversed by TNFα.Science advances · 2026Article
- Exploring the interactions of integrins and CEACAM6 (Review).Experimental and therapeutic medicine · 2025Review
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- Spatial transcriptomics of glioblastoma defines biologically and clinically significant reprogramming patterns across unique spatial microenvironments.bioRxiv : the preprint server for biology · 2025Article
- Identifying survival subtypes with autoencoder using multiple types of high-dimensional genomic data from studies of glioblastoma multiforme.Briefings in bioinformatics · 2025Article
- Signaling pathways as the pivotal regulators of cisplatin resistance in tumor cells through SOX2 upregulation.Medical oncology (Northwood, London, England) · 2025Review
- Spatial epigenomic niches underlie glioblastoma cell state plasticity.bioRxiv : the preprint server for biology · 2025Article
- Analysis of ABCC3 in glioma progression: implications for prognosis, immunotherapy, and drug resistance.Discover oncology · 2025Article
- Emerging roles of angiopoietin‑like 4 in human tumors (Review).International journal of oncology · 2025Review
- ANGPTL4-the Link Binding Lipid Metabolism and Inflammation.Current medicinal chemistry · 2025Review
- Toxicity profiles of immune checkpoint inhibitors in nervous system cancer: a comprehensive disproportionality analysis using FDA adverse event reporting system.Clinical and experimental medicine · 2024Article
- Review
- Potential role of ANGPTL4 in cancer progression, metastasis, and metabolism: a brief review.BMB reports · 2024Review
- Potential Effects of Low-Level Toluene Exposure on the Nervous System of Mothers and Infants.International journal of molecular sciences · 2024Article
- ANGPTL4 regulates ovarian cancer progression by activating the ERK1/2 pathway.Cancer cell international · 2024Article
- Article
- ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1.Journal of translational medicine · 2024Article
- Adipocyte regulation of cancer stem cells.Cancer science · 2023Review
- CNS tumor stroma transcriptomics identify perivascular fibroblasts as predictors of immunotherapy resistance in glioblastoma patients.NPJ genomic medicine · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Glioblastoma (GBM) is the most aggressive type of brain tumor, with strong invasiveness and a high tolerance to chemotherapy. Despite the current standard treatment combining temozolomide (TMZ) and radiotherapy, glioblastoma can be incurable due to drug resistance. The existence of glioma stem-like cells (GSCs) is considered the major reason for drug resistance. However, the mechanism of GSC enrichment remains unclear. Herein, we found that the expression and secretion of angiopoietin-like 4 protein (ANGPTL4) were clearly increased in GSCs. The overexpression of ANGPTL4 induced GSC enrichment that was characterized by polycomb complex protein BMI-1 and SRY (sex determining region Y)-box 2 (SOX2) expression, resulting in TMZ resistance in GBM. Furthermore, epidermal growth factor receptor (EGFR) phosphorylation induced 4E-BP1 phosphorylation that was required for ANGPTL4-induced GSC enrichment. In particular, ANGPTL4 induced 4E-BP1 phosphorylation by activating phosphoinositide 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase (ERK) cascades for inducing stemness. To elucidate the mechanism contributing to ANGPTL4 upregulation in GSCs, chromatin immunoprecipitation coupled with sequencing (ChIP-Seq) revealed that specificity protein 4 (Sp4) was associated with the promoter region, -979 to -606, and the luciferase reporter assay revealed that Sp4 positively regulated activity of the ANGPTL4 promoter. Moreover, both ANGPTL4 and Sp4 were highly expressed in GBM and resulted in a poor prognosis. Taken together, Sp4-mediated ANGPTL4 upregulation induces GSC enrichment through the EGFR/AKT/4E-BP1 cascade.
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