ArticleBMC cancer2014
FTY720 inhibits proliferation and epithelial-mesenchymal transition in cholangiocarcinoma by inactivating STAT3 signaling.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Article
- Role of the PP2A Pathway in Cholangiocarcinoma: State of the Art and Future Perspectives.Cancers · 2022Article
- Targeting Epithelial-to-Mesenchymal Transition in Radioresistance: Crosslinked Mechanisms and Strategies.Frontiers in oncology · 2022Review
- TargetingCancers · 2021Article
- Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.Cancers · 2021Review
- Therapeutic potential of Fingolimod in triple negative breast cancer preclinical models.Translational oncology · 2021Article
- Fingolimod inhibits multiple stages of the HIV-1 life cycle.PLoS pathogens · 2020Article
- Long non‑coding RNA ZEB1‑AS1 predicts a poor prognosis and promotes cancer progression through the miR‑200a/ZEB1 signaling pathway in intrahepatic cholangiocarcinoma.International journal of oncology · 2020Article
- Common transcriptional programs and the role of chemokine (C-C motif) ligand 20 (EXCLI journal · 2020Article
- S1PR1 as a Novel Promising Therapeutic Target in Cancer Therapy.Molecular diagnosis & therapy · 2019Review
- EVI‑1 acts as an oncogene and positively regulates calreticulin in breast cancer.Molecular medicine reports · 2019Article
- The mechanism of ATF3 repression of epithelial-mesenchymal transition and suppression of cell viability in cholangiocarcinoma via p53 signal pathway.Journal of cellular and molecular medicine · 2019Article
- Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell Survival and Tumor Growth.Translational oncology · 2019Article
- FTY720 Decreases Tumorigenesis in Group 3 Medulloblastoma Patient-Derived Xenografts.Scientific reports · 2018Article
- Signaling pathways and mesenchymal transition in pediatric high-grade glioma.Cellular and molecular life sciences : CMLS · 2018Review
- New Directions in the Study and Treatment of Metastatic Cancer.Frontiers in oncology · 2018Review
- FTY720 Induces Autophagy-Associated Apoptosis in Human Oral Squamous Carcinoma Cells, in Part, through a Reactive Oxygen Species/Mcl-1-Dependent Mechanism.Scientific reports · 2017Article
- Knockout of the Nogo-B Gene Attenuates Tumor Growth and Metastasis in Hepatocellular Carcinoma.Neoplasia (New York, N.Y.) · 2017Article
- Effects of long term low- and high-dose sodium arsenite exposure in human transitional cells.American journal of translational research · 2017Article
- Stattic Enhances Radiosensitivity and Reduces Radio-Induced Migration and Invasion in HCC Cell Lines through an Apoptosis Pathway.BioMed research international · 2017Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInterleukin 6 (IL-6)-mediated signal transducers and activators of transcription 3 (STAT-3) phosphorylation (activation) is aberrantly sustained in cholangiocarcinoma cells resulting in enhanced myeloid cell leukemia 1 (Mcl-1) expression and resistance to apoptosis. FTY720, a new immunosuppressant, derived from ISP-1, has been studied for its putative anti-cancer properties. This study aimed to elucidate the mechanism by which FTY720 mediates antitumor effects in cholangiocarcinoma (CC) cells.
methodsThree CC cell lines were examined, QBC939, TFK-1, and HuCCT1. The therapeutic effects of FTY720 were evaluated in vitro and in vivo. Cell proliferation, apoptosis, cell cycle, invasive potential, and epithelial- mesenchy-mal transition (EMT) were examined.
resultsFTY720 greatly inhibited CC cells proliferation and EMT in vitro and in vivo, and this effect was associated with dephosphorylation of STAT3tyr705. FTY720 induced apoptosis and G1 phase arrest in CC cells, and inhibited invasion of CC cells. Western blot analysis showed that FTY720 induced cleavage of caspases 3, 8 and 9, and of PARP, in a dose-dependent manner, consistent with a substantial decrease in p-STAT3, Bcl-xL, Bcl-2, survivin, cyclin D1, cyclin E, N-cadherin, vimentin, VEGF and TWIST1. In vivo studies showed that tumor growth and metastasis were significantly suppressed after FTY720 treatment.
conclusionsThese results suggest that FTY720 induces a significant decrease in p-STAT3, which inhibits proliferation and EMT of CC cells, and then induces G1 phase arrest and apoptosis. We have characterized a novel immunosuppressant, which shows potential anti-tumor effects on CC via p-STAT3 inhibition. FTY720 merits further investigation and warrants clinical evaluation.
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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.