ArticleOncogene2015
CCN5/WISP-2 promotes growth arrest of triple-negative breast cancer cells through accumulation and trafficking of p27(Kip1) via Skp2 and FOXO3a regulation.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Gambogic acid suppresses osteosarcoma progression through upregulation of FOXO3a.Discover oncology · 2025Article
- Oxidative DNA damage promotes vascular ageing associated with changes in extracellular matrix-regulating proteins.Cardiovascular research · 2025Article
- Role and regulation of FOXO3a: new insights into breast cancer therapy.Frontiers in pharmacology · 2024Review
- The role of CCNs in controlling cellular communication in the tumor microenvironment.Journal of cell communication and signaling · 2023Review
- The carboxyl-terminal TSP1-homology domain is the biologically active effector peptide of matricellular protein CCN5 that counteracts profibrotic CCN2.The Journal of biological chemistry · 2023Article
- [Lowered expression of CCN5 in endometriotic tissues promotes proliferation, migration and invasion of endometrial stromal cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- CCN5 activation by free or encapsulated EGCG is required to render triple-negative breast cancer cell viability and tumor progression.Pharmacology research & perspectives · 2021Article
- CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment.Frontiers in genetics · 2021Review
- WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells.Journal of ovarian research · 2020Article
- Emerging Roles of Matricellular Proteins in Systemic Sclerosis.International journal of molecular sciences · 2020Review
- WISP2 exhibits its potential antitumor activity via targeting ERK and E-cadherin pathways in esophageal cancer cells.Journal of experimental & clinical cancer research : CR · 2019Article
- MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/AKT pathway.Cell death & disease · 2019Article
- Foxo3a-dependent miR-633 regulates chemotherapeutic sensitivity in gastric cancer by targeting Fas-associated death domain.RNA biology · 2019Article
- The emerging role of WISP proteins in tumorigenesis and cancer therapy.Journal of translational medicine · 2019Review
- Racial disparity in breast cancer: can it be mattered for prognosis and therapy.Journal of cell communication and signaling · 2018Review
- Leptin-induced ER-α-positive breast cancer cell viability and migration is mediated by suppressing CCN5-signaling via activating JAK/AKT/STAT-pathway.BMC cancer · 2018Article
- CCN5/WISP-2 restores ER-∝ in normal and neoplastic breast cells and sensitizes triple negative breast cancer cells to tamoxifen.Oncogenesis · 2017Article
- Deficiency of CCN5/WISP-2-Driven Program in breast cancer Promotes Cancer Epithelial cells to mesenchymal stem cells and Breast Cancer growth.Scientific reports · 2017Article
- Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells via SKP2/P27 signaling pathway.Scientific reports · 2017Article
- Dual roles of CCN proteins in breast cancer progression.Journal of cell communication and signaling · 2016Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The matricellular protein CCN5/WISP-2 represents a promising target in triple-negative breast cancer (TNBC) because treatment or induced activation of CCN5 in TNBC cells promotes cell growth arrest at the G0/G1 phase, reduces cell proliferation and delays tumor growth in the xenograft model. Our studies found that the p27(Kip1) tumor suppressor protein is upregulated and relocalized to the nucleus from cytoplasm by CCN5 in these cells and that these two events (upregulation and relocalization of p27(Kip1)) are critical for CCN5-induced growth inhibition of TNBC cells. In the absence of CCN5, p27(Kip1) resides mostly in the cytoplasm, which is associated with the aggressive nature of cancer cells. Mechanistically, CCN5 inhibits Skp2 expression, which seems to stabilize the p27(Kip1) protein in these cells. On the other hand, CCN5 also recruits FOXO3a to mediate the transcriptional regulation of p27(Kip1). The recruitment of FOXO3a is achieved by the induction of its expression and activity through shifting from cytoplasm to the nucleus. Our data indicate that CCN5 blocks PI3K/AKT signaling to dephosphorylate at S318, S253 and Thr32 in FOXO3a for nuclear relocalization and activation of FOXO3a. Moreover, inhibition of α6β1 receptors diminishes CCN5 action on p27(Kip1) in TNBC cells. Collectively, these data suggest that CCN5 effectively inhibits TNBC growth through the accumulation and trafficking of p27(Kip1) via Skp2 and FOXO3a regulation, and thus, activation of CCN5 may have the therapeutic potential to kill TNBC.
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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.