ArticleCancer research2010
Blockade of CCN6 (WISP3) activates growth factor-independent survival and resistance to anoikis in human mammary epithelial cells.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- Circulating CCN6/WISP3 in type 2 diabetes mellitus patients and its correlation with insulin resistance and inflammation: statistical and machine learning analyses.BMC medical informatics and decision making · 2025Article
- The matricellular protein CCN6 differentially regulates mitochondrial metabolism in normal epithelium and in metaplastic breast carcinomas.Journal of cell communication and signaling · 2022Article
- Molecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment.Scientific reports · 2021Article
- Liver cancer: WISP3 suppresses hepatocellular carcinoma progression by negative regulation of β-catenin/TCF/LEF signalling.Cell proliferation · 2019Article
- The emerging role of WISP proteins in tumorigenesis and cancer therapy.Journal of translational medicine · 2019Review
- CCN6 regulates IGF2BP2 and HMGA2 signaling in metaplastic carcinomas of the breast.Breast cancer research and treatment · 2018Article
- Matricellular CCN6 (WISP3) protein: a tumor suppressor for mammary metaplastic carcinomas.Journal of cell communication and signaling · 2018Review
- MMTV-cre;Ccn6 knockout mice develop tumors recapitulating human metaplastic breast carcinomas.Oncogene · 2017Article
- Article
- CCN6: a modulator of breast cancer progression.Journal of cell communication and signaling · 2016Review
- The matricellular protein CCN6 (WISP3) decreases Notch1 and suppresses breast cancer initiating cells.Oncotarget · 2016Article
- Matricellular proteins of the Cyr61/CTGF/NOV (CCN) family and the nervous system.Frontiers in cellular neuroscience · 2015Review
- PROX1 gene is differentially expressed in oral cancer and reduces cellular proliferation.Medicine · 2014Article
- Silencing of WISP3 suppresses gastric cancer cell proliferation and metastasis and inhibits Wnt/β-catenin signaling.International journal of clinical and experimental pathology · 2014Article
- The CCN family proteins: modulators of bone development and novel targets in bone-associated tumors.BioMed research international · 2014Review
- CCN6: a novel method of aTAKing cancer.Journal of cell communication and signaling · 2013Article
- Dysfunction of collagen synthesis and secretion in chondrocytes induced by wisp3 mutation.International journal of endocrinology · 2013Article
- CCN6 knockdown disrupts acinar organization of breast cells in three-dimensional cultures through up-regulation of type III TGF-β receptor.Neoplasia (New York, N.Y.) · 2012Article
- On how CCN6 suppresses breast cancer growth and invasion.Journal of cell communication and signaling · 2012Article
- Matricellular proteins: a sticky affair with cancers.Journal of oncology · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
CCN6 is a secreted cysteine-rich matricellular protein (36.9 kDa) that exerts growth-inhibitory functions in breast cancer. Reduction or loss of CCN6 protein has been reported in invasive carcinomas of the breast with lymph node metastasis and in inflammatory breast cancer. However, the mechanism by which CCN6 loss promotes breast cancer growth remains to be defined. In the present study, we developed lentiviral-mediated short hairpin RNA CCN6 knockdown (KD) in nontumorigenic mammary epithelial cells MCF10A and HME. We discovered that CCN6 KD protects mammary epithelial cells from apoptosis and activates growth factor-independent survival. In the absence of exogenous growth factors, CCN6 KD was able to promote growth under anchorage-independent conditions and triggered resistance to detachment-induced cell death (anoikis). On serum starvation, CCN6 KD was sufficient for activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Growth factor-independent cell survival was stunted in CCN6 KD cells when treated with either human recombinant CCN6 protein or the PI3K inhibitor LY294002. Targeted inhibition of Akt isoforms revealed that the survival advantage rendered by CCN6 KD requires specific activation of Akt-1. The relevance of our studies to human breast cancer is highlighted by the finding that low CCN6 protein levels are associated with upregulated expression of phospho-Akt-1 (Ser(473)) in 21% of invasive breast carcinomas. These results enable us to pinpoint one mechanism by which CCN6 controls survival of breast cells mediated by the PI3K/Akt-1 pathway.
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Registered trials
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.