ArticleOncotarget2016
The matricellular protein CCN6 (WISP3) decreases Notch1 and suppresses breast cancer initiating cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Molecular Consequences ofInternational journal of molecular sciences · 2025Article
- Noninvasive Mapping of Extracellular Potassium in Breast Tumors via Multi-Wavelength Photoacoustic Imaging.Sensors (Basel, Switzerland) · 2025Article
- CCN6 Suppresses Metaplastic Breast Carcinoma by Antagonizing Wnt/β-Catenin Signaling to Inhibit EZH2-Driven EMT.Cancer research · 2024Article
- CCN proteins: opportunities for clinical studies-a personal perspective.Journal of cell communication and signaling · 2023Review
- The matricellular protein CCN6 differentially regulates mitochondrial metabolism in normal epithelium and in metaplastic breast carcinomas.Journal of cell communication and signaling · 2022Article
- Mesenchymal stromal cells from a progressive pseudorheumatoid dysplasia patient show altered osteogenic differentiation.European journal of medical research · 2022Article
- CCN1 promotes hepatic steatosis and inflammation in non-alcoholic steatohepatitis.Scientific reports · 2020Article
- Skeletal phenotype/genotype in progressive pseudorheumatoid chondrodysplasia.Clinical rheumatology · 2020Article
- Controversies around epithelial-mesenchymal plasticity in cancer metastasis.Nature reviews. Cancer · 2019Review
- The emerging role of WISP proteins in tumorigenesis and cancer therapy.Journal of translational medicine · 2019Review
- Notch Signaling Activation as a Hallmark for Triple-Negative Breast Cancer Subtype.Journal of oncology · 2019Review
- CCN6-mediated MMP-9 activation enhances metastatic potential of human chondrosarcoma.Cell death & disease · 2018Article
- Matricellular CCN6 (WISP3) protein: a tumor suppressor for mammary metaplastic carcinomas.Journal of cell communication and signaling · 2018Review
- Article
- MMTV-cre;Ccn6 knockout mice develop tumors recapitulating human metaplastic breast carcinomas.Oncogene · 2017Article
- Dual roles of CCN proteins in breast cancer progression.Journal of cell communication and signaling · 2016Article
- CCN family of proteins: critical modulators of the tumor cell microenvironment.Journal of cell communication and signaling · 2016Article
- CCN6: a modulator of breast cancer progression.Journal of cell communication and signaling · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Increasing evidence supports that the epithelial to mesenchymal transition (EMT) in breast cancer cells generates tumor initiating cells (TICs) but the contribution of the tumor microenvironment to these programs needs further elucidation. CCN6 (WISP3) is a secreted matrix-associated protein (36.9 kDa) of the CCN family (named after CTGF, Cyr61 and Nov) that is reduced or lost in invasive carcinomas of the breast with lymph node metastasis and in inflammatory breast cancer. CCN6 exerts breast cancer growth and invasion inhibitory functions, but the mechanisms remain to be defined. In the present study we discovered that ectopic CCN6 overexpression in triple negative (TN) breast cancer cells and in cells derived from patients is sufficient to induce a mesenchymal to epithelial transition (MET) and to reduce TICs. In vivo, CCN6 overexpression in the TIC population of MDA-MB-231 cells delayed tumor initiation, reduced tumor volume, and inhibited the development of metastasis. Our studies reveal a novel CCN6/Slug signaling axis that regulates Notch1 signaling activation, epithelial cell phenotype and breast TICs, which requires the conserved thrombospondin type 1 (TSP1) motif of CCN6. The relevance of these data to human breast cancer is highlighted by the finding that CCN6 protein levels are inversely correlated with Notch1 intracellular activated form (NICD1) in 69.5% of invasive breast carcinomas. These results demonstrate that CCN6 regulates epithelial and mesenchymal states transition and TIC programs, and pinpoint one responsible mechanism.
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