ArticleNeoplasia (New York, N.Y.)2012
CCN6 knockdown disrupts acinar organization of breast cells in three-dimensional cultures through up-regulation of type III TGF-β receptor.
Article in Neoplasia (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Noninvasive Mapping of Extracellular Potassium in Breast Tumors via Multi-Wavelength Photoacoustic Imaging.Sensors (Basel, Switzerland) · 2025Article
- The matricellular protein CCN6 differentially regulates mitochondrial metabolism in normal epithelium and in metaplastic breast carcinomas.Journal of cell communication and signaling · 2022Article
- A reproducible scaffold-free 3D organoid model to study neoplastic progression in breast cancer.Journal of cell communication and signaling · 2019Article
- The emerging role of WISP proteins in tumorigenesis and cancer therapy.Journal of translational medicine · 2019Review
- 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
- Usp9x regulates Ets-1 ubiquitination and stability to control NRAS expression and tumorigenicity in melanoma.Nature communications · 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
- H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TβR3 in placentae with fetal growth restriction.Oncotarget · 2016Article
- The matricellular protein CCN6 (WISP3) decreases Notch1 and suppresses breast cancer initiating cells.Oncotarget · 2016Article
- WISP3 is highly expressed in a subset of colorectal carcinomas with a better prognosis.OncoTargets and therapy · 2016Article
- Eyeing the Cyr61/CTGF/NOV (CCN) group of genes in development and diseases: highlights of their structural likenesses and functional dissimilarities.Human genomics · 2015Review
- Characterization of type III TGF-β receptor expression in invasive breast carcinomas: a potential new marker and target for triple negative breast cancer.Journal of cell communication and signaling · 2014Article
- Article
- Three dimensional cultures: a tool to study normal acinar architecture vs. malignant transformation of breast cells.Journal of visualized experiments : JoVE · 2014Article
- Cancer subclonal genetic architecture as a key to personalized medicine.Neoplasia (New York, N.Y.) · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
While normal cells in the human breast are organized into acinar structures, disruption of the acinar architecture is a hallmark of cancer. In a three-dimensional model of morphogenesis, we show that down-regulation of the matrix-associated tumor suppressor protein CCN6 (WNT1-inducible-signaling pathway protein 3) disrupts breast epithelial cell polarity and organization into acini through up-regulation of the type III transforming growth factor-β receptor (TβRIII or betaglycan). Down-regulation of CCN6 in benign breast cells led to loss of tissue polarity and resulted in cellular disorganization with loss of α6 integrin-rich basement membrane and the basolateral polarity protein E-cadherin. Silencing of TβRIII with shRNA and siRNA rescued the ability of breast epithelial cells to form polarized acinar structures with reduced matrix invasion and restored the correct expression of α6 integrin and E-cadherin. Conversely, CCN6 overexpression in aggressive breast cancer cells reduced TβRIII in vitro and in a xenograft model of CCN6 overexpression. The relevance of our studies to human breast cancer is highlighted by the finding that CCN6 protein levels are inversely associated with TβRIII protein in 64%of invasive breast carcinomas. These results reveal a novel function of the matricellular protein CCN6 and establish a mechanistic link between CCN6 and TβRIII in maintaining acinar organization in the breast.
Indexed as
Identifiers
What OpenQuestion holds
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.