ArticleOncogene2013
Krüppel-like factor 4 (KLF4) suppresses neuroblastoma cell growth and determines non-tumorigenic lineage differentiation.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development.Neuro-oncology · 2025Article
- Alternative splicing of KLF4 in myeloid cells: implications for cellular plasticity and trained immunity in cancer and inflammatory disease.Frontiers in immunology · 2025Review
- Article
- Differences and Similarities between Colorectal Cancer Cells and Colorectal Cancer Stem Cells: Molecular Insights and Implications.ACS omega · 2023Article
- New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy.Seminars in cancer biology · 2023Review
- Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma.Oxidative medicine and cellular longevity · 2023Article
- Pluripotent Stem Cells: Cancer Study, Therapy, and Vaccination.Stem cell reviews and reports · 2021Review
- Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting.World journal of stem cells · 2021Review
- C1q/TNF-Related Protein 9 Attenuates Atherosclerosis by Inhibiting Hyperglycemia-Induced Endothelial Cell Senescence Through the AMPKα/KLF4 Signaling Pathway.Frontiers in pharmacology · 2021Article
- KLF4-mediated upregulation of CD9 and CD81 suppresses hepatocellular carcinoma development via JNK signaling.Cell death & disease · 2020Article
- KLF4 functions as an oncogene in promoting cancer stem cell-like characteristics in osteosarcoma cells.Acta pharmacologica Sinica · 2019Article
- Emerging roles of Myc in stem cell biology and novel tumor therapies.Journal of experimental & clinical cancer research : CR · 2018Review
- Graphene Oxide-Silver Nanoparticles Nanocomposite Stimulates Differentiation in Human Neuroblastoma Cancer Cells (SH-SY5Y).International journal of molecular sciences · 2017Article
- Article
- DNA-Methyltransferase 1 Induces Dedifferentiation of Pancreatic Cancer Cells through Silencing of Krüppel-Like Factor 4 Expression.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Krüppel-like factors in mammalian stem cells and development.Development (Cambridge, England) · 2017Review
- Krüppel-like Factor 4 Blocks Hepatocellular Carcinoma Dedifferentiation and Progression through Activation of Hepatocyte Nuclear Factor-6.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- The Transcription Regulator Krüppel-Like Factor 4 and Its Dual Roles of Oncogene in Glioblastoma and Tumor Suppressor in Neuroblastoma.Forum on immunopathological diseases and therapeutics · 2016Article
- A distinct gene expression signature characterizes human neuroblastoma cancer stem cells.Stem cell research · 2015Article
- Functional interplay between MYCN, NCYM, and OCT4 promotes aggressiveness of human neuroblastomas.Cancer science · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastoma (NB) is an embryonal tumor and possesses a unique propensity to exhibit either a spontaneous regression or an unrestrained growth. However, the underlying mechanism for this paradoxical clinical outcome remains largely unclear. Quantitative RT-PCR analysis on 102 primary NB tumors revealed that lower Krüppel-like factor 4 (KLF4) expression is frequently found in the unfavorable NB (Mann-Whitney test, P=0.027). In particular with the high-risk factors such as age of patient >1 year, MYCN amplification and low TRKA expression, the decreased expression of KLF4 was significantly associated with an unfavorable NB outcome. Despite knockdown of KLF4 alone is not sufficient to increase tumorigenicity of NB cells in vivo, stable expression of KLF4 short hairpin RNA in Be(2)-C cells significantly promoted growth of NB cells and inhibited cell differentiation toward fibromuscular lineage. In concordant with these observations, overexpression of KLF4 in SH-SY-5Y cells profoundly suppressed cell proliferation by direct upregulation of cell-cycle inhibitor protein p21(WAF1/CIP1), and knocking down p21(WAF1/CIP1) could partially rescue the suppressive effect of KLF4. Importantly, KLF4 overexpressing cells have lost their neuroblastic phenotypes, they were epithelial-like, strongly substrate-adherent, expressing smooth muscle marker and became non-tumorigenic, suggesting that KLF4 expression is crucial for lineage determination of NB cells, probably, favoring spontaneous tumor regression. Subsequent global gene expression profiling further revealed that transforming growth factor beta (TGFβ) and cell-cycle pathways are highly dysregulated upon KLF4 overexpression, and myogenic modulators, MEF2A and MYOD1 were found significantly upregulated. Taken together, we have demonstrated that KLF4 contributes to the favorable disease outcome by directly mediating the growth and lineage determination of NB cells.
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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.