ArticleOncogene2011
Activation of Notch1 signaling in stromal fibroblasts inhibits melanoma growth by upregulating WISP-1.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Targeting Melanoma-Associated Fibroblasts to Overcome Cancer Stem Cell-Driven Drug Resistance.Journal of the American College of Surgeons · 2026Article
- WISP1 Inhibits Hepatocellular Carcinoma Cell Proliferation by Promoting CyclinD1 Ubiquitination and Downregulating its Expression.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- A Comprehensive Exploration of Agents Targeting Tumor Microenvironment: Challenges and Future Perspectives.Journal of immunotherapy and precision oncology · 2024Review
- An overview of CCN4 (WISP1) role in human diseases.Journal of translational medicine · 2024Review
- Fibroblasts as Turned Agents in Cancer Progression.Cancers · 2023Review
- Metastasis and cancer associated fibroblasts: taking it up a NOTCH.Frontiers in cell and developmental biology · 2023Review
- Reprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling.Cellular & molecular immunology · 2022Article
- Notch signaling in the pathogenesis, progression and identification of potential targets for cholangiocarcinoma (Review).Molecular and clinical oncology · 2022Review
- The Effects of WISP1 Polymorphisms on the Prognosis of Lung Cancer Patients with Platinum-Based Chemotherapy.Pharmacogenomics and personalized medicine · 2021Article
- E-Selectin-Overexpressing Mesenchymal Stem Cell Therapy Confers Improved Reperfusion, Repair, and Regeneration in a Murine Critical Limb Ischemia Model.Frontiers in cardiovascular medicine · 2021Article
- Gangrene, revascularization, and limb function improved with E-selectin/adeno-associated virus gene therapy.JVS-vascular science · 2021Article
- Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity.PloS one · 2021Article
- Notch1 signaling determines the plasticity and function of fibroblasts in diabetic wounds.Life science alliance · 2020Article
- Cell Communication Network Factor 4 (CCN4/WISP1) Shifts Melanoma Cells from a Fragile Proliferative State to a Resilient Metastatic State.Cellular and molecular bioengineering · 2020Article
- The Role of Dermal Fibroblasts in Nevoid Basal Cell Carcinoma Syndrome Patients: An Overview.International journal of molecular sciences · 2020Review
- Intracellular Notch1 Signaling in Cancer-Associated Fibroblasts Dictates the Plasticity and Stemness of Melanoma Stem/Initiating Cells.Stem cells (Dayton, Ohio) · 2019Article
- WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial-mesenchymal transition.The Journal of biological chemistry · 2019Article
- The emerging role of WISP proteins in tumorigenesis and cancer therapy.Journal of translational medicine · 2019Review
- Dual effect of WISP-1 in diverse pathological processes.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2016Article
- Notch1-WISP-1 axis determines the regulatory role of mesenchymal stem cell-derived stromal fibroblasts in melanoma metastasis.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor microenvironment is emerging as an important target for cancer therapy. Fibroblasts (Fbs) within the tumor stroma are critically involved in promoting tumor growth and angiogenesis through secretion of soluble factors, synthesis of extracellular matrix and direct cell-cell interaction. In this work, we aim to alter the biological activity of stromal Fbs by modulating the Notch1 signaling pathway. We show that Fbs engineered to constitutively activate the Notch1 pathway significantly inhibit melanoma growth and tumor angiogenesis. We determine that the inhibitory effect of 'Notch-engineered' Fbs is mediated by increased secretion of Wnt-induced secreted protein-1 (WISP-1) as the effects of Notch1 activation in Fbs are reversed by shRNA-mediated blockade of WISP-1. When 'Notch-engineered' Fbs are co-grafted with melanoma cells in SCID mice, shRNA-mediated blockade of WISP-1 reverses the tumor-suppressive phenotype of the 'Notch-engineered' Fbs, significantly increases melanoma growth and tumor angiogenesis. Consistent with these findings, supplement of recombinant WISP-1 protein inhibits melanoma cell growth in vitro. In addition, WISP-1 is modestly expressed in melanoma-activated Fbs but highly expressed in inactivated Fbs. Evaluation of human melanoma skin biopsies indicates that expression of WISP-1 is significantly lower in melanoma nests and surrounding areas filled with infiltrated immune cells than in the adjacent dermis unaffected by the melanoma. Overall, our study shows that constitutive activation of the Notch1 pathway confers Fbs with a suppressive phenotype to melanoma growth, partially through WISP-1. Thus, targeting tumor stromal Fbs by activating Notch signaling and/or increasing WISP-1 may represent a novel therapeutic approach to combat melanoma.
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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.