ArticleProceedings of the National Academy of Sciences of the United States of America2015
p63 Sustains self-renewal of mammary cancer stem cells through regulation of Sonic Hedgehog signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 157 citations in OpenAlex.
- Three-dimensional spheroid models in breast cancer: tumor microenvironment complexity, cancer stem cell-driven resistance, and translational model integration.Journal of translational medicine · 2026Review
- Dynamics, function, and regulation of mammary stem cells in development and disease.Experimental & molecular medicine · 2026Review
- WWOX maintains epidermal identity and suppresses EMT to prevent aggressive cutaneous squamous cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- p63 and ZNF148 cooperate to regulate head and neck squamous cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ΔNp63 bookmarks and creates an accessible epigenetic environment for TGFβ-induced cancer cell stemness and invasiveness.Cell communication and signaling : CCS · 2024Article
- ΔNp63α-mediated epigenetic regulation in keratinocyte senescence.Epigenetics · 2023Article
- p63: a crucial player in epithelial stemness regulation.Oncogene · 2023Review
- A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient.Cell death discovery · 2023Article
- A primary luminal/HER2 negative breast cancer patient with mismatch repair deficiency.Cell death discovery · 2023Article
- A network map of cytoskeleton-associated protein 4 (CKAP4) mediated signaling pathway in cancer.Journal of cell communication and signaling · 2023Article
- Bovine milk-derived cells express transcriptome markers of pluripotency and secrete bioactive factors with regenerative and antimicrobial activity.Scientific reports · 2023Article
- Type 2 inflammation drives an airway basal stem cell program through insulin receptor substrate signaling.The Journal of allergy and clinical immunology · 2023Article
- Signaling pathways governing the maintenance of breast cancer stem cells and their therapeutic implications.Frontiers in cell and developmental biology · 2023Review
- The dual role of p63 in cancer.Frontiers in oncology · 2023Review
- ΔNp63/p73 drive metastatic colonization by controlling a regenerative epithelial stem cell program in quasi-mesenchymal cancer stem cells.Developmental cell · 2022Article
- Possible Involvement of the Upregulation of ΔNp63 Expression Mediated by HER2-Activated Aryl Hydrocarbon Receptor in Mammosphere Maintenance.International journal of molecular sciences · 2022Article
- Long non-coding RNAs affecting cell metabolism in cancer.Biology direct · 2022Review
- Breast Cancer Stem Cells: Signaling Pathways, Cellular Interactions, and Therapeutic Implications.Cancers · 2022Review
- ΔNp63-Senataxin circuit controls keratinocyte differentiation by promoting the transcriptional termination of epidermal genes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- BRD4 regulates the induction and maintenance of cancer stem cells in squamous cell carcinoma.Stem cell investigation · 2022Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
The predominant p63 isoform, ΔNp63, is a master regulator of normal epithelial stem cell (SC) maintenance. However, in vivo evidence of the regulation of cancer stem cell (CSC) properties by p63 is still limited. Here, we exploit the transgenic MMTV-ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2) mouse model of carcinogenesis to dissect the role of p63 in the regulation of mammary CSC self-renewal and breast tumorigenesis. ErbB2 tumor cells enriched for SC-like properties display increased levels of ΔNp63 expression compared with normal mammary progenitors. Down-regulation of p63 in ErbB2 mammospheres markedly restricts self-renewal and expansion of CSCs, and this action is fully independent of p53. Furthermore, transplantation of ErbB2 progenitors expressing shRNAs against p63 into the mammary fat pads of syngeneic mice delays tumor growth in vivo. p63 knockdown in ErbB2 progenitors diminishes the expression of genes encoding components of the Sonic Hedgehog (Hh) signaling pathway, a driver of mammary SC self-renewal. Remarkably, p63 regulates the expression of Sonic Hedgehog (Shh), GLI family zinc finger 2 (Gli2), and Patched1 (Ptch1) genes by directly binding to their gene regulatory regions, and eventually contributes to pathway activation. Collectively, these studies highlight the importance of p63 in maintaining the self-renewal potential of mammary CSCs via a positive modulation of the Hh signaling pathway.
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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.