ArticleCellular oncology (Dordrecht, Netherlands)2013
Stat6 cooperates with Sp1 in controlling breast cancer cell proliferation by modulating the expression of p21(Cip1/WAF1) and p27 (Kip1).
Article in Cellular oncology (Dordrecht, Netherlands), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Engineering IL-4 resistant proinflammatory human myeloid cells for cancer immunotherapy.Molecular oncology · 2026Article
- STAT family of transcription factors in breast cancer: Pathogenesis and therapeutic opportunities and challenges.Seminars in cancer biology · 2022Review
- Farnesiferol C Exerts Antiproliferative Effects on Hepatocellular Carcinoma HepG2 Cells by Instigating ROS-Dependent Apoptotic Pathway.Pharmaceuticals (Basel, Switzerland) · 2022Article
- STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis.Frontiers in oncology · 2022Article
- IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1.International journal of molecular sciences · 2021Article
- Umbelliferone Ameliorates Benign Prostatic Hyperplasia by Inhibiting Cell Proliferation and G1/S Phase Cell Cycle Progression through Regulation of STAT3/E2F1 Axis.International journal of molecular sciences · 2021Article
- EML4-ALK-mediated activation of the JAK2-STAT pathway is critical for non-small cell lung cancer transformation.BMC pulmonary medicine · 2021Article
- HMGB1 orchestrates STING-mediated senescence via TRIM30α modulation in cancer cells.Cell death discovery · 2021Article
- ARHGAP24 inhibits cell proliferation and cell cycle progression and induces apoptosis of lung cancer via a STAT6-WWP2-p27 axis.Carcinogenesis · 2020Article
- Prognostic value of key genes of the JAK-STAT signaling pathway in patients with cutaneous melanoma.Oncology letters · 2020Article
- Metformin and Breast Cancer: Molecular Targets.Journal of mammary gland biology and neoplasia · 2019Review
- New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating Sestrin-2 in human bladder cancer.Cancer letters · 2018Article
- PVT1-derived miR-1207-5p promotes breast cancer cell growth by targeting STAT6.Cancer science · 2017Article
- STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia.Cell death & disease · 2016Article
- Tumor growth suppressive effect of IL-4 through p21-mediated activation of STAT6 in IL-4Rα overexpressed melanoma models.Oncotarget · 2016Article
- Downregulation of RNF128 Predicts Progression and Poor Prognosis in Patients with Urothelial Carcinoma of the Upper Tract and Urinary Bladder.Journal of Cancer · 2016Article
- The Role of Sulforaphane in Epigenetic Mechanisms, Including Interdependence between Histone Modification and DNA Methylation.International journal of molecular sciences · 2015Review
- PC-TraFF: identification of potentially collaborating transcription factors using pointwise mutual information.BMC bioinformatics · 2015Article
- Fine-scale mapping of the 4q24 locus identifies two independent loci associated with breast cancer risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2015Article
- Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting lipolysis.Journal of lipid research · 2014Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe signal transducer and activator of transcription 6 (Stat6), a member of the family of DNA-binding proteins, has been identified as a critical cell differentiation modulator in breast cancer cells. As of yet, the mechanisms underlying this function have remained largely unknown. To further elucidate the role of Stat6 in breast cancer development, we investigated the consequences of exogenous Stat6 expression.
methodsProliferation assays and flow cytometry assays were conducted to evaluate the putative role of Stat6 on cell proliferation. To this end, we produced synchronized cells after a double thymidine block, as confirmed by FACS analysis. mRNA levels of Stat6 were measured by RNase protection analysis. To confirm the interaction among proteins, we employed GST pull-down assays and immunoprecipitation assays. Luciferase assays and ChIP assays were used to assess the transcriptional activity.
resultsCompared to control breast cancer cells, we found that exogenous Stat6 expression plays a critical role in controlling cell proliferation. Also in different breast tumor cell lines, endogenous Stat6 expression was found to be positively related to a lower proliferation rate. Interestingly, in human breast cancer cells Stat6 functions in G1/S cell cycle progression, and the growth-inhibitory effect of Stat6 was shown to be mediated by induction of the G1 cyclin-dependent kinase inhibitors p21(Cip1/WAF1) (p21) and p27(Kip1) (p27). Simultaneously, G1-related cyclin/cyclin-dependent kinase activities and pRB phosphorylation were markedly reduced, and cell cycle progression was blocked in the G1 phase. Stat6 knockdown resulted in enhanced cell proliferation and a decrease in p21 and p27 mRNA levels in the steroid-responsive and non-responsive T-47D and MDA-MB-231 cell lines, respectively. In addition, the stimulatory effect of Stat6 on p21 and p27 gene transcription was found to be associated with interaction of Stat6 with the transcription factor Sp1 at the proximal Sp1-binding sites in their respective promoters.
conclusionsTogether, these results identify Stat6 as an important cell differentiation regulatory protein functioning, at least in part, by interacting with Sp1 to activate the p21 and p27 gene promoters in breast cancer cells.
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