ArticleProceedings of the National Academy of Sciences of the United States of America2012
Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 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.
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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
28 citing papers in PubMed, 46 citations in OpenAlex.
- TFCP2 Fusion-Positive Rhabdomyosarcomas: A Report of 10 Cases and a Review of the Literature.Cancers · 2025Article
- Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression.Cancer discovery · 2023Article
- A Cell-Penetrant Peptide Disrupting the Transcription Factor CP2c Complexes Induces Cancer-Specific Synthetic Lethality.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges.Molecules (Basel, Switzerland) · 2022Review
- Pharmacologic Manipulation of Late SV40 Factor Suppresses Wnt Signaling and Inhibits Growth of Allogeneic and Syngeneic Colon Cancer Xenografts.The American journal of pathology · 2022Article
- Article
- Factor quinolinone inhibitors alter cell morphology and motility by destabilizing interphase microtubules.Scientific reports · 2021Article
- Astrocyte elevated gene-1 (AEG-1): A key driver of hepatocellular carcinoma (HCC).Advances in cancer research · 2021Review
- Epithelioid and spindle cell rhabdomyosarcoma with FUS-TFCP2 or EWSR1-TFCP2 fusion: report of two cases.Virchows Archiv : an international journal of pathology · 2020Review
- Article
- The microtubule-associated histone methyltransferase SET8, facilitated by transcription factor LSF, methylates α-tubulin.The Journal of biological chemistry · 2020Article
- Grainyhead-like transcription factors in cancer - Focus on recent developments.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Expanding the Spectrum of Intraosseous Rhabdomyosarcoma: Correlation Between 2 Distinct Gene Fusions and Phenotype.The American journal of surgical pathology · 2019Article
- Targeting the SET and RING-associated (SRA) domain of ubiquitin-like, PHD and ring finger-containing 1 (UHRF1) for anti-cancer drug development.Oncotarget · 2018Review
- Structural basis of gene regulation by the Grainyhead/CP2 transcription factor family.Nucleic acids research · 2018Article
- TFCP2 activates beta-catenin/TCF signaling in the progression of pancreatic cancer.Oncotarget · 2017Article
- Glucose Deficiency Elevates Acid-Sensing Ion Channel 2a Expression and Increases Seizure Susceptibility in Temporal Lobe Epilepsy.Scientific reports · 2017Article
- FQI1: a transcription-methylation switch for cancer.Oncotarget · 2017Article
- TFCP2 Genetic Polymorphism Is Associated with Predisposition to and Transplant Prognosis of Hepatocellular Carcinoma.Gastroenterology research and practice · 2017Article
- Transcription factor LSF-DNMT1 complex dissociation by FQI1 leads to aberrant DNA methylation and gene expression.Oncotarget · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Despite the prevalence of HCC, there is no effective, systemic treatment. The transcription factor LSF is a promising protein target for chemotherapy; it is highly expressed in HCC patient samples and cell lines, and promotes oncogenesis in rodent xenograft models of HCC. Here, we identify small molecules that effectively inhibit LSF cellular activity. The lead compound, factor quinolinone inhibitor 1 (FQI1), inhibits LSF DNA-binding activity both in vitro, as determined by electrophoretic mobility shift assays, and in cells, as determined by ChIP. Consistent with such inhibition, FQI1 eliminates transcriptional stimulation of LSF-dependent reporter constructs. FQI1 also exhibits antiproliferative activity in multiple cell lines. In LSF-overexpressing cells, including HCC cells, cell death is rapidly induced; however, primary or immortalized hepatocytes are unaffected by treatment with FQI1. The highly concordant structure-activity relationship of a panel of 23 quinolinones strongly suggests that the growth inhibitory activity is due to a single biological target or family. Coupled with the striking agreement between the concentrations required for antiproliferative activity (GI(50)s) and for inhibition of LSF transactivation (IC(50)s), we conclude that LSF is the specific biological target of FQIs. Based on these in vitro results, we tested the efficacy of FQI1 in inhibiting HCC tumor growth in a mouse xenograft model. As a single agent, tumor growth was dramatically inhibited with no observable general tissue cytotoxicity. These findings support the further development of LSF inhibitors for cancer chemotherapy.
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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.