ArticleCancer research2008
The high-mobility group A1a/signal transducer and activator of transcription-3 axis: an achilles heel for hematopoietic malignancies?
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 103 citations in OpenAlex.
- Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia.Leukemia & lymphoma · 2011Trial
- EDNRB-dependent endothelin signaling reduces proliferation and promotes proneural-to-mesenchymal transition in gliomas.Molecular oncology · 2026Article
- LMO2 regulates STAT3 localization to the nucleus in breast cancer cells.microPublication biology · 2026Article
- High Mobility Group A1 Chromatin Keys: Unlocking the Genome During MPN Progression.International journal of molecular sciences · 2025Review
- HMGA1 acts as an epigenetic gatekeeper of ASCL2 and Wnt signaling during colon tumorigenesis.The Journal of clinical investigation · 2025Article
- Loss of OVOL2 in Triple-Negative Breast Cancer Promotes Fatty Acid Oxidation Fueling Stemness Characteristics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Excessive tubulin glutamylation leads to progressive cone-rod dystrophy and loss of outer segment integrity.Human molecular genetics · 2024Article
- Dynamic phenotypic reprogramming and chemoresistance induced by lung fibroblasts in small cell lung cancer.Scientific reports · 2024Article
- Cyclic fasting bolsters cholesterol biosynthesis inhibitors' anticancer activity.Nature communications · 2023Article
- Cancer-associated fibroblasts promote cancer stemness by inducing expression of the chromatin-modifying protein CBX4 in squamous cell carcinoma.Carcinogenesis · 2023Article
- HMGA1 induces FGF19 to drive pancreatic carcinogenesis and stroma formation.The Journal of clinical investigation · 2023Article
- Article
- Novel treatment strategy for NRAS-mutated melanoma through a selective inhibitor of CD147/VEGFR-2 interaction.Oncogene · 2022Article
- MTAP loss correlates with an immunosuppressive profile in GBM and its substrate MTA stimulates alternative macrophage polarization.Scientific reports · 2022Article
- High Mobility Group A1 (HMGA1): Structure, Biological Function, and Therapeutic Potential.International journal of biological sciences · 2022Review
- BRD4 Regulates Transcription Factor ΔNp63α to Drive a Cancer Stem Cell Phenotype in Squamous Cell Carcinomas.Cancer research · 2021Article
- Suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability.Disease models & mechanisms · 2021Article
- HMGA1, Moonlighting Protein Function, and Cellular Real Estate: Location, Location, Location!Biomolecules · 2021Review
- Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells.Journal of cellular and molecular medicine · 2021Article
- Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF-1α-independent VEGF expression and angiogenesis in hepatocellular carcinoma.British journal of pharmacology · 2020Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 7 institutions in 1 country.
Funding
Abstract
Although HMGA1 (high-mobility group A1; formerly HMG-I/Y) is an oncogene that is widely overexpressed in aggressive cancers, the molecular mechanisms underlying transformation by HMGA1 are only beginning to emerge. HMGA1 encodes the HMGA1a and HMGA1b protein isoforms, which function in regulating gene expression. To determine how HMGA1 leads to neoplastic transformation, we looked for genes regulated by HMGA1 using gene expression profile analysis. Here, we show that the STAT3 gene, which encodes the signaling molecule signal transducer and activator of transcription 3 (STAT3), is a critical downstream target of HMGA1a. STAT3 mRNA and protein are up-regulated in fibroblasts overexpressing HMGA1a and activated STAT3 recapitulates the transforming activity of HMGA1a in fibroblasts. HMGA1a also binds directly to a conserved region of the STAT3 promoter in vivo in human leukemia cells by chromatin immunoprecipitation and activates transcription of the STAT3 promoter in transfection experiments. To determine if this pathway contributes to HMGA1-mediated transformation, we investigated STAT3 expression in our HMGA1a transgenic mice, all of which developed aggressive lymphoid malignancy. STAT3 expression was increased in the leukemia cells from our transgenics but not in control cells. Blocking STAT3 function induced apoptosis in the transgenic leukemia cells but not in controls. In primary human leukemia samples, there was a positive correlation between HMGA1a and STAT3 mRNA. Moreover, blocking STAT3 function in human leukemia or lymphoma cells led to decreased cellular motility and foci formation. Our results show that the HMGA1a-STAT3 axis is a potential Achilles heel that could be exploited therapeutically in hematopoietic and other malignancies overexpressing HMGA1a.
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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.