ArticleCancer medicine2019
Nr5a2 promotes cancer stem cell properties and tumorigenesis in nonsmall cell lung cancer by regulating Nanog.
Article in Cancer medicine, 2019. 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, 32 citations in OpenAlex.
- Single nuclei and spatial profiling of sacrococcygeal teratomas reveals cellular composition and X inactivation heterogeneity.NPJ precision oncology · 2026Article
- Epigenetic regulation of NR5A2 influences colorectal cancer cell stemness via a stemness-related transcription factor NANOG.Cell communication and signaling : CCS · 2025Article
- Unraveling the molecular-pathological characteristics and cellular complexity of the tumor immune microenvironment in metastatic non-small cell lung cancer.Cell communication and signaling : CCS · 2025Review
- Abnormal phosphorylation of human LRH1 at Ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinoma.BMC cancer · 2025Article
- Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.Endocrinology · 2025Review
- TC2N maintains stem cell-like characteristics to accelerate lung carcinogenesis by blockade of dual specificity protein phosphatase 3.Cell & bioscience · 2025Article
- MFAP5 Strengthened the Stem Cell Features of Non-small Cell Lung Cancer Cells by Regulating the FBW/Sox9 Axis.Current pharmaceutical biotechnology · 2025Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Article
- Clinical relevance of stem cells in lung cancer.World journal of stem cells · 2023Review
- Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Nuclear receptor NR5A2 negatively regulates cell proliferation and tumor growth in nervous system malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- NR5A2 transcriptional activation by BRD4 promotes pancreatic cancer progression by upregulating GDF15.Cell death discovery · 2021Article
- PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas.Oncogenesis · 2021Article
- Cancer stem cells: a major culprit of intra-tumor heterogeneity.American journal of cancer research · 2021Review
- LRH1 Acts as an Oncogenic Driver in Human Osteosarcoma and Pan-Cancer.Frontiers in cell and developmental biology · 2021Article
- Characteristics of the PI3K/AKT and MAPK/ERK pathways involved in the maintenance of self-renewal in lung cancer stem-like cells.International journal of biological sciences · 2021Article
- NR5A2 Is One of 12 Transcription Factors Predicting Prognosis in HNSCC and Regulates Cancer Cell Proliferation in a p53-Dependent Manner.Frontiers in oncology · 2021Article
- Cancer Stemness-Based Prognostic Immune-Related Gene Signatures in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.Frontiers in endocrinology · 2021Article
- Expression patterns and clinical significance of the potential cancer stem cell markers OCT4 and NANOG in colorectal cancer patients.Molecular & cellular oncology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer has the highest mortality rate due to late diagnosis and high incidence of metastasis. Cancer stem cells (CSCs) are a subgroup of cancer cells with self-renewal capability similar to that of normal stem cells (NSCs). While CSCs may play an important role in cancer progression, mechanisms underlying CSC self-renewal and the relationship between self-renewal of the NSCs and CSCs remain elusive. The orphan nuclear receptor Nr5a2 is a transcriptional factor, and a regulator of stemness of embryonic stem cells and induced pluripotent stem cells. However, whether Nr5a2 regulates the self-renewal of lung CSCs is unknown. Here, we showed the diagnostic and prognostic values of elevated Nr5a2 expression in human lung cancer. We generated the mouse LLC-SD lung carcinoma CSC cellular model in which Nr5a2 expression was enhanced. Using the LLC-SD model, through transient and stable siRNA interference of Nr5a2 expression, we provided convincing evidence for a regulatory role of Nr5a2 in the maintenance of lung CSC self-renewal and stem cell properties in vitro. Further, using the syngeneic and orthotopic lung transplantation model, we elucidated augmented cancer biological properties associated with Nr5a2 promotion of LLC-SD self-renewal. More importantly, we revealed that Nr5a2's regulatory role in promoting LLC-SD self-renewal is mediated by transcriptional activation of its direct target Nanog. Taken together, in this study, we have provided convincing evidence in vitro and in vivo demonstrating that Nr5a2 can induce lung CSC properties and promote tumorigenesis and progression through transcriptional up-regulation of Nanog.
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