ArticleThe Journal of biological chemistry2012
The matricellular protein CCN1/Cyr61 is a critical regulator of Sonic Hedgehog in pancreatic carcinogenesis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Article
- CCN1-induced senescence and dysfunction of umbilical cord blood endothelial colony-forming cells in the pathogenesis of preeclampsia.Frontiers in endocrinology · 2026Article
- CCN1 as a compartment-specific biomarker of active microenvironmental remodeling: evidence from bone repair, aging, inflammation, and cancer.Frontiers in medicine · 2026Review
- Targeted nanoencapsulation of tunicamycin reduces toxicity while improving its therapeutic effectiveness in pancreatic cancer cells.Molecular therapy. Oncology · 2025Article
- Myeloid CCN3 protects against aortic valve calcification.Cell communication and signaling : CCS · 2023Article
- Redox-Regulation in Cancer Stem Cells.Biomedicines · 2022Review
- CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation.Nature communications · 2022Article
- Recent advances in understanding pancreatic cancer.Faculty reviews · 2022Review
- Review
- Quercetin suppresses pancreatic ductal adenocarcinoma progression via inhibition of SHH and TGF-β/Smad signaling pathways.Cell biology and toxicology · 2021Article
- Notch in mechanotransduction - from molecular mechanosensitivity to tissue mechanostasis.Journal of cell science · 2020Review
- Downregulation of miR-506-3p Facilitates EGFR-TKI Resistance through Induction of Sonic Hedgehog Signaling in Non-Small-Cell Lung Cancer Cell Lines.International journal of molecular sciences · 2020Article
- Conjunction junction, what's the function? CCN proteins as targets in fibrosis and cancers.American journal of physiology. Cell physiology · 2020Review
- Article
- Caught between a "Rho" and a hard place: are CCN1/CYR61 and CCN2/CTGF the arbiters of microvascular stiffness?Journal of cell communication and signaling · 2020Review
- Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma.Journal of cell communication and signaling · 2019Article
- A novel triazole, NMK-T-057, induces autophagic cell death in breast cancer cells by inhibiting γ-secretase-mediated activation of Notch signaling.The Journal of biological chemistry · 2019Article
- KRAS, YAP, and obesity in pancreatic cancer: A signaling network with multiple loops.Seminars in cancer biology · 2019Review
- Cyr61 overexpression induced by interleukin 8 via NF-kB signaling pathway and its role in tumorigenesis of gastric carcinoma in vitro.International journal of clinical and experimental pathology · 2019Article
- The MAZ transcription factor is a downstream target of the oncoprotein Cyr61/CCN1 and promotes pancreatic cancer cell invasion via CRAF-ERK signaling.The Journal of biological chemistry · 2018Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CCN1 is a matricellular protein and a member of the CCN family of growth factors. CCN1 is associated with the development of various cancers including pancreatic ductal adenocarcinoma (PDAC). Our recent studies found that CCN1 plays a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. CCN1 mRNA and protein were detected in the early precursor lesions, and their expression intensified with disease progression. However, biochemical activity and the molecular targets of CCN1 in pancreatic cancer cells are unknown. Here we show that CCN1 regulates the Sonic Hedgehog (SHh) signaling pathway, which is associated with the PDAC progression and poor prognosis. SHh regulation by CCN1 in pancreatic cancer cells is mediated through the active Notch-1. Notably, active Notch-1is recruited by CCN1 in these cells via the inhibition of proteasomal degradation results in stabilization of the receptor. We find that CCN1-induced activation of SHh signaling might be necessary for CCN1-dependent in vitro pancreatic cancer cell migration and tumorigenicity of the side population of pancreatic cancer cells (cancer stem cells) in a xenograft in nude mice. Moreover, the functional role of CCN1 could be mediated through the interaction with the αvβ3 integrin receptor. These extensive studies propose that targeting CCN1 can provide a new treatment option for patients with pancreatic cancer since blocking CCN1 simultaneously blocks two critical pathways (i.e. SHh and Notch1) associated with the development of the disease as well as drug resistance.
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