ArticleCancer biology & therapy2009
Epithelial transformation by KLF4 requires Notch1 but not canonical Notch1 signaling.
Article in Cancer biology & therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Pooled it
- miR-449a: A Promising Biomarker and Therapeutic Target in Cancer and Other Diseases.Cell biochemistry and biophysics · 2024Review
- Jagged1-Notch1-deployed tumor perivascular niche promotes breast cancer stem cell phenotype through Zeb1.Nature communications · 2020Article
- KLF3 is a crucial regulator of metastasis by controlling STAT3 expression in lung cancer.Molecular carcinogenesis · 2019Article
- Chemotherapy-Induced Extracellular Vesicle miRNAs Promote Breast Cancer Stemness by TargetingCancer research · 2019Article
- Multifactorial Contribution of Notch Signaling in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2019Review
- MicroRNA-10b regulates epithelial-mesenchymal transition by modulating KLF4/Notch1/E-cadherin in cisplatin-resistant nasopharyngeal carcinoma cells.American journal of cancer research · 2016Article
- Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells.PLoS pathogens · 2015Article
- New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers.World journal of clinical cases · 2014Review
- The transcription factor KLF4 as an independent predictive marker for pathologic complete remission in breast cancer neoadjuvant chemotherapy: a case-control study.OncoTargets and therapy · 2014Article
- Promoter hypermethylation of KLF4 inactivates its tumor suppressor function in cervical carcinogenesis.PloS one · 2014Article
- Non-canonical notch signaling in cancer and immunity.Frontiers in oncology · 2014Review
- Regulation of EMT by KLF4 in gastrointestinal cancer.Current cancer drug targets · 2013Review
- Krüppel-like factors in cancer.Nature reviews. Cancer · 2013Review
- cAMP-responsive element modulator α (CREMα) contributes to decreased Notch-1 expression in T cells from patients with active systemic lupus erythematosus (SLE).The Journal of biological chemistry · 2012Article
- A KLF4-miRNA-206 autoregulatory feedback loop can promote or inhibit protein translation depending upon cell context.Molecular and cellular biology · 2011Article
- Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion.Oncogene · 2011Article
- Krüppel-like family of transcription factor 9, a differentiation-associated transcription factor, suppresses Notch1 signaling and inhibits glioblastoma-initiating stem cells.Stem cells (Dayton, Ohio) · 2011Article
- Mammalian Krüppel-like factors in health and diseases.Physiological reviews · 2010Review
- Non-canonical activation of Notch signaling/target genes in vertebrates.Cellular and molecular life sciences : CMLS · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The transcription factors Notch1 and KLF4 specify epithelial cell fates and confer stem cell properties. Suggesting a functional relationship, each gene can act to promote or suppress tumorigenesis in a context-dependent manner, and alteration of KLF4 or Notch pathway genes in mice gives rise to similar phenotypes. Activation of a conditional allele of KLF4 in RK3E epithelial cells rapidly induces expression of Notch1 mRNA and the active, intracellular form of Notch1. KLF4-induced transformation was suppressed by knockdown of endogenous Notch1 using siRNA or an inhibitor of gamma-secretase. Chromatin immunoprecipitation assay shows that KLF4 binds to the proximal Notch1 promoter in human mammary epithelial cells, and siRNA-mediated suppression of KLF4 in human mammary cancer cells results in reduced expression of Notch1. Furthermore, KLF4 and Notch1 expression are correlated in primary human breast tumors (N = 89; Pearson analysis, r > 0.5, p < 0.0001). Like KLF4, Notch1 was previously shown to induce transformation of rat cells immortalized with adenovirus E1A, similar to RK3E cells. We therefore compared the signaling requirements for Notch1- or KLF4-induced malignant transformation of RK3E. As expected, transformation by Notch1 was suppressed by dominant-negative CSL or MAML1, inhibitors of canonical Notch1 signaling. However, these inhibitors did not suppress transformation by KLF4. Therefore, while KLF4-induced transformation requires Notch1, canonical Notch1 signaling is not required, and Notch1 may signal through a distinct pathway in cells with increased KLF4 activity. These results suggest that KLF4 could contribute to breast tumor progression by activating synthesis of Notch1 and by promoting signaling through a non-canonical Notch1 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.