ArticleProceedings of the National Academy of Sciences of the United States of America2024
The exostosin glycosyltransferase 1/STAT3 axis is a driver of breast cancer aggressiveness.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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
6 citing papers in PubMed, 7 citations in OpenAlex.
- Combined FAK and MEK inhibition suppresses chromosome 8 gain malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- Tumor promotion or suppression: Revisiting the role of EXT1 and Heparan sulfate.Histology and histopathology · 2026Review
- Multi-Omics and Single-Cell Dissection of Exostosin Glycosyltransferases (EXT1/EXT2) Reveals Divergent Oncogenic Roles and Therapeutic Vulnerabilities in Gliomas.Journal of Cancer · 2026Article
- EXT1 and Its Methylation Involved in the Progression of Uterine Corpus Endometrial Carcinoma Pathogenesis.Applied biochemistry and biotechnology · 2025Article
- Epithelial-mesenchymal transition status is a remarkable biomarker for the combination treatment with avutometinib and defactinib in KRAS-mutated non-small cell lung cancer.British journal of cancer · 2024Article
- The role of ncRNAs and exosomes in the development and progression of endometrial cancer.Frontiers in oncology · 2024Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The epithelial-mesenchymal transition (EMT) program is crucial for transforming carcinoma cells into a partially mesenchymal state, enhancing their chemoresistance, migration, and metastasis. This shift in cell state is tightly regulated by cellular mechanisms that are not yet fully characterized. One intriguing EMT aspect is the rewiring of the proteoglycan landscape, particularly the induction of heparan sulfate proteoglycan (HSPG) biosynthesis. This proteoglycan functions as a co-receptor that accelerates cancer-associated signaling pathways through its negatively-charged residues. However, the precise mechanisms through which EMT governs HSPG biosynthesis and its role in cancer cell plasticity remain elusive. Here, we identified exostosin glycosyltransferase 1 (EXT1), a central enzyme in HSPG biosynthesis, to be selectively upregulated in aggressive tumor subtypes and cancer cell lines, and to function as a key player in breast cancer aggressiveness. Notably, ectopic expression of EXT1 in epithelial cells is sufficient to induce HSPG levels and the expression of known mesenchymal markers, subsequently enhancing EMT features, including cell migration, invasion, and tumor formation. Additionally, EXT1 loss in MDA-MB-231 cells inhibits their aggressiveness-associated traits such as migration, chemoresistance, tumor formation, and metastasis. Our findings reveal that EXT1, through its role in HSPG biosynthesis, governs signal transducer and activator of transcription 3 (STAT3) signaling, a known regulator of cancer cell aggressiveness. Collectively, we present the EXT1/HSPG/STAT3 axis as a central regulator of cancer cell plasticity that directly links proteoglycan synthesis to oncogenic signaling pathways.
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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 Socratic graph.