ArticleOncotarget2017
A screen for Fli-1 transcriptional modulators identifies PKC agonists that induce erythroid to megakaryocytic differentiation and suppress leukemogenesis.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Vitamin D3 and its active form calcitriol suppress erythroleukemia through upregulation of CHAC1 and downregulation of NOTCH1.Medical oncology (Northwood, London, England) · 2025Article
- Role of Transcription Factor Fli-1 in Inflammation and Autoimmune Diseases.Biomolecules · 2025Review
- FLI1 Induces Plaque Psoriasis and Its Inhibition Attenuates Disease Progression.Journal of inflammation research · 2025Article
- FLI-1-driven regulation of endothelial cells in human diseases.Journal of translational medicine · 2024Review
- An intricate regulatory circuit between FLI1 and GATA1/GATA2/LDB1/ERG dictates erythroid vs. megakaryocytic differentiation.Molecular medicine reports · 2024Article
- FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression.BMC cancer · 2024Article
- Lovastatin inhibits erythroleukemia progression through KLF2-mediated suppression of MAPK/ERK signaling.BMC cancer · 2023Article
- FLI1 Regulates Histamine Decarboxylase Expression to Control Inflammation Signaling and Leukemia Progression.Journal of inflammation research · 2023Article
- Cooperative ETS Transcription Factors Enforce Adult Endothelial Cell Fate and Cardiovascular Homeostasis.Nature cardiovascular research · 2022Article
- Current insights into the role of Fli-1 in hematopoiesis and malignant transformation.Cellular and molecular life sciences : CMLS · 2022Review
- FLI1 Induces Megakaryopoiesis Gene Expression Through WAS/WIP-Dependent and Independent Mechanisms; Implications for Wiskott-Aldrich Syndrome.Frontiers in immunology · 2021Article
- A C21-steroidal derivative suppresses T-cell lymphoma in mice by inhibiting SIRT3 via SAP18-SIN3.Communications biology · 2020Article
- Article
- Fli-1 Activation through Targeted Promoter Activity Regulation Using a Novel 3', 5'-diprenylated Chalcone Inhibits Growth and Metastasis of Prostate Cancer Cells.International journal of molecular sciences · 2020Article
- FLI1 promotes protein translation via the transcriptional regulation of MKNK1 expression.International journal of oncology · 2020Article
- Selective ERK1/2 agonists isolated from Melia azedarach with potent anti-leukemic activity.BMC cancer · 2019Article
- Identification of diterpenoid compounds that interfere with Fli-1 DNA binding to suppress leukemogenesis.Cell death & disease · 2019Article
- An Explorer of Chemical Biology of Plant Natural Products in Southwest China, Xiaojiang Hao.Natural products and bioprospecting · 2018Review
- Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect.International journal of oncology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ETS-related transcription factor Fli-1 affects many developmental programs including erythroid and megakaryocytic differentiation, and is frequently de-regulated in cancer. Fli-1 was initially isolated following retrovirus insertional mutagenesis screens for leukemic initiator genes, and accordingly, inhibition of this transcription factor can suppress leukemia through induction of erythroid differentiation. To search for modulators of Fli-1, we hereby performed repurposing drug screens with compounds isolated from Chinese medicinal plants. We identified agents that can transcriptionally activate or inhibit a Fli-1 reporter. Remarkably, agents that increased Fli-1 transcriptional activity conferred a strong anti-cancer activity upon Fli-1-expressing leukemic cells in culture. As opposed to drugs that suppress Fli1 activity and lead to erythroid differentiation, growth suppression by these new Fli-1 transactivating compounds involved erythroid to megakaryocytic conversion (EMC). The identified compounds are structurally related to diterpene family of small molecules, which are known agonists of protein kinase C (PKC). In accordance, these PKC agonists (PKCAs) induced PKC phosphorylation leading to activation of the mitogen-activated protein kinase (MAPK) pathway, increased cell attachment and EMC, whereas pharmacological inhibition of PKC or MAPK diminished the effect of our PKCAs. Moreover, in a mouse model of leukemia initiated by Fli-1 activation, the PKCA compounds exhibited strong anti-cancer activity, which was accompanied by increased presence of CD41/CD61 positive megakaryocytic cells in leukemic spleens. Thus, PKC agonists offer a novel approach to combat Fli-1-induced leukemia, and possibly other cancers,by inducing EMC in part through over-activation of the PKC-MAPK-Fli-1 pathway.
Indexed as
Identifiers
What 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.