ArticleAmerican journal of cancer research2022
Eltrombopag binds SDC4 directly and enhances MAPK signaling and macropinocytosis in cancer cells.
Article in American journal of cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- Andrographolide targets syndecan4 to impair its interaction with syntenin and inhibits the biogenesis of small extracellular vesicles.The Journal of biological chemistry · 2026Article
- Identification of non-oncology drugs with activity against inflammatory and triple-negative breast cancer cell lines.Oncology letters · 2026Article
- Syndecan-4 promotes gastric cancer progression through activating TGF-β1 induced lipid reprogramming and contributes positive loop circuits.Discover oncology · 2025Article
- SDC4 identified as an oncogenic target gene of NF-κB in TNFα-Induced tumor cells.Scientific reports · 2025Article
- Multiomics profiling identifies the poor prognostic role of a tumor cluster with GNA15 overexpression in triple-negative breast cancer.Frontiers in immunology · 2025Article
- A bioinformatics analysis and an experimental validation of the hypoxia-related prognostic model.Journal of gastrointestinal oncology · 2023Article
- Tubeimoside-2 Triggers Methuosis in Hepatocarcinoma Cells through the MKK4-p38α Axis.Pharmaceutics · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Syndecan-4 (SDC4) is a single-pass transmembrane glycoprotein implicated in a variety of oncogenic signaling pathways. It is also an intrinsically disordered protein and considered "undruggable". In the present study, we confirmed that knocking out SDC4 in pancreatic cancer cells markedly impaired macropinocytosis, colony formation, as well as xenograft tumor initiation and growth. Quantitative proteomic profiling of Sdc4 knockout (KO) cells revealed significant changes in cell metabolic pathways. In a cellular protein-based ligand interaction screening, we identified that Eltrombopag (ETBP), an FDA-approved agonist of the thrombopoietin receptor (TPOR) for immune thrombocytopenia, could directly bind to SDC4 with a Kd value of ~2 µM. We showed that the transmembrane motif was essential for SDC4 binding to ETBP. Unexpectedly, ETBP not only increased SDC4 abundance, but also enhanced SDC4-associated MAPK signaling pathway and macropinocytosis in cancer cells. Our results indicate that ETBP is a potential agonist of SDC4 in a fashion similar to its original target TPOR, and that caution should be taken when using ETBP for chemotherapy-induced thrombocytopenia in cancer patients.
Indexed as
Identifiers
35812066PMC9251693W4285048808What OpenQuestion holds
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.