ArticleCancer research2016
ΔNp63α Silences a miRNA Program to Aberrantly Initiate a Wound-Healing Program That Promotes TGFβ-Induced Metastasis.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- A network map of cytoskeleton-associated protein 4 (CKAP4) mediated signaling pathway in cancer.Journal of cell communication and signaling · 2023Article
- The p53 Family Members p63 and p73 Roles in the Metastatic Dissemination: Interactions with microRNAs and TGFβ Pathway.Cancers · 2022Review
- Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis.Experimental & molecular medicine · 2022Article
- HPV-mediated regulation of SMAD4 modulates the DNA damage response in head and neck cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Article
- Research models and mesenchymal/epithelial plasticity of osteosarcoma.Cell & bioscience · 2021Review
- Targeting of ΔNp63α by miR-522 promotes the migration of breast epithelial cells.FEBS open bio · 2021Article
- Osteosarcoma and Metastasis.Frontiers in oncology · 2021Review
- Circular RNA hsa_circ_0001306 Functions as a Competing Endogenous RNA to Regulate FBXW7 Expression by Sponging miR-527 in Hepatocellular Carcinoma.Journal of Cancer · 2021Article
- Article
- TBRG4 Knockdown Suppresses Proliferation and Growth of Human Osteosarcoma Cell Lines MG63 Through PI3K/Akt Pathway.OncoTargets and therapy · 2020Article
- miRNA Regulation of Glutathione Homeostasis in Cancer Initiation, Progression and Therapy Resistance.MicroRNA (Shariqah, United Arab Emirates) · 2020Review
- miRNA signatures in childhood sarcomas and their clinical implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis.International journal of molecular sciences · 2019Review
- miR-665 expression predicts poor survival and promotes tumor metastasis by targeting NR4A3 in breast cancer.Cell death & disease · 2019Article
- Somatic Mutations in miRNA Genes in Lung Cancer-Potential Functional Consequences of Non-Coding Sequence Variants.Cancers · 2019Article
- p63 at the Crossroads between Stemness and Metastasis in Breast Cancer.International journal of molecular sciences · 2019Review
- ΔNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment.Molecular oncology · 2019Review
- Review
- Synergistic antitumour activity of HDAC inhibitor SAHA and EGFR inhibitor gefitinib in head and neck cancer: a key role for ΔNp63α.British journal of cancer · 2019Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Primary cancer cell dissemination is a key event during the metastatic cascade, but context-specific determinants of this process remain largely undefined. Multiple reports have suggested that the p53 (TP53) family member p63 (TP63) plays an antimetastatic role through its minor epithelial isoform containing the N-terminal transactivation domain (TAp63). However, the role and contribution of the major p63 isoform lacking this domain, ΔNp63α, remain largely undefined. Here, we report a distinct and TAp63-independent mechanism by which ΔNp63α-expressing cells within a TGFβ-rich microenvironment become positively selected for metastatic dissemination. Orthotopic transplantation of ΔNp63α-expressing human osteosarcoma cells into athymic mice resulted in larger and more frequent lung metastases than transplantation of control cells. Mechanistic investigations revealed that ΔNp63α repressed miR-527 and miR-665, leading to the upregulation of two TGFβ effectors, SMAD4 and TβRII (TGFBR2). Furthermore, we provide evidence that this mechanism reflects a fundamental role for ΔNp63α in the normal wound-healing response. We show that ΔNp63α-mediated repression of miR-527/665 controls a TGFβ-dependent signaling node that switches off antimigratory miR-198 by suppressing the expression of the regulatory factor, KSRP (KHSRP). Collectively, these findings reveal that a novel miRNA network involved in the regulation of physiologic wound-healing responses is hijacked and suppressed by tumor cells to promote metastatic dissemination. Cancer Res; 76(11); 3236-51. ©2016 AACR.
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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.