ArticlePloS one2014
Both canonical and non-canonical Wnt signaling independently promote stem cell growth in mammospheres.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Radiation therapy for triple-negative breast cancer: emerging role of microRNAs as biomarkers and radiosensitivity modifiers. A systematic review.Breast cancer research and treatment · 2022Pooled it
- Wnt signaling - using the bloodstream to send a message.Cellular and molecular life sciences : CMLS · 2025Review
- Wnt Signaling Inhibitors as Therapeutic Approach in Ischemic Heart Disease.Molecules (Basel, Switzerland) · 2024Review
- WNT Signaling in Stem Cells: A Look into the Non-Canonical Pathway.Stem cell reviews and reports · 2024Review
- Signaling pathways governing the maintenance of breast cancer stem cells and their therapeutic implications.Frontiers in cell and developmental biology · 2023Review
- Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets.Cancer cell international · 2022Review
- The role of Wnt signalling in development of coronary artery disease and its risk factors.Open biology · 2020Review
- Aberrant WNT/CTNNB1 Signaling as a Therapeutic Target in Human Breast Cancer: Weighing the Evidence.Frontiers in cell and developmental biology · 2020Review
- Article
- Down-regulation of FZD3 receptor suppresses growth and metastasis of human melanoma independently of canonical WNT signaling.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Aberrant Wnt Signaling Pathway in the Hematopoietic Stem/Progenitor Compartment in Experimental Leukemic Animal.Journal of cell communication and signaling · 2019Article
- Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription.Cell death & disease · 2018Article
- Article
- Ell3 stimulates 5-FU resistance in a breast cancer cell line.Oncology letters · 2017Article
- Diverse regulation of mammary epithelial growth and branching morphogenesis through noncanonical Wnt signaling.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Wnt5a Signaling in Normal and Cancer Stem Cells.Stem cells international · 2017Review
- Microvesicle-mediated Wnt/β-Catenin Signaling Promotes Interspecies Mammary Stem/Progenitor Cell Growth.The Journal of biological chemistry · 2016Article
- Molecular Mechanisms of Obesity-Induced Osteoporosis and Muscle Atrophy.Frontiers in physiology · 2016Review
- Promising Druggable Target in Head and Neck Squamous Cell Carcinoma: Wnt Signaling.Frontiers in pharmacology · 2016Review
- Canonical and noncanonical Wnt signaling in neural stem/progenitor cells.Cellular and molecular life sciences : CMLS · 2015Review
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2 authors.
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Abstract
The characterization of mammary stem cells, and signals that regulate their behavior, is of central importance in understanding developmental changes in the mammary gland and possibly for targeting stem-like cells in breast cancer. The canonical Wnt/β-catenin pathway is a signaling mechanism associated with maintenance of self-renewing stem cells in many tissues, including mammary epithelium, and can be oncogenic when deregulated. Wnt1 and Wnt3a are examples of ligands that activate the canonical pathway. Other Wnt ligands, such as Wnt5a, typically signal via non-canonical, β-catenin-independent, pathways that in some cases can antagonize canonical signaling. Since the role of non-canonical Wnt signaling in stem cell regulation is not well characterized, we set out to investigate this using mammosphere formation assays that reflect and quantify stem cell properties. Ex vivo mammosphere cultures were established from both wild-type and Wnt1 transgenic mice and were analyzed in response to manipulation of both canonical and non-canonical Wnt signaling. An increased level of mammosphere formation was observed in cultures derived from MMTV-Wnt1 versus wild-type animals, and this was blocked by treatment with Dkk1, a selective inhibitor of canonical Wnt signaling. Consistent with this, we found that a single dose of recombinant Wnt3a was sufficient to increase mammosphere formation in wild-type cultures. Surprisingly, we found that Wnt5a also increased mammosphere formation in these assays. We confirmed that this was not caused by an increase in canonical Wnt/β-catenin signaling but was instead mediated by non-canonical Wnt signals requiring the receptor tyrosine kinase Ror2 and activity of the Jun N-terminal kinase, JNK. We conclude that both canonical and non-canonical Wnt signals have positive effects promoting stem cell activity in mammosphere assays and that they do so via independent signaling mechanisms.
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