ArticleOncotarget2016
Notch1-WISP-1 axis determines the regulatory role of mesenchymal stem cell-derived stromal fibroblasts in melanoma metastasis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting Melanoma-Associated Fibroblasts to Overcome Cancer Stem Cell-Driven Drug Resistance.Journal of the American College of Surgeons · 2026Article
- The interplay of cancer-associated fibroblasts and apoptotic cancer cells suppresses lung cancer cell growth through WISP-1-integrin ανβ3-STAT1 signaling pathway.Cell communication and signaling : CCS · 2025Article
- Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cells.Cell communication and signaling : CCS · 2025Article
- Roles of Non-Coding RNA in Anthracycline Cardiotoxicity: A Narrative Review.Journal of inflammation research · 2025Review
- Reprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling.Cellular & molecular immunology · 2022Article
- Mechanistic Interrogation of Cell Transformation In Vitro: The Transformics Assay as an Exemplar of Oncotransformation.International journal of molecular sciences · 2022Article
- The CCN axis in cancer development and progression.Journal of cell communication and signaling · 2021Review
- Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity.PloS one · 2021Article
- The Role of Cancer-Associated Fibroblast as a Dynamic Player in Mediating Cancer Stemness in the Tumor Microenvironment.Frontiers in cell and developmental biology · 2021Review
- Notch1 signaling determines the plasticity and function of fibroblasts in diabetic wounds.Life science alliance · 2020Article
- 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
- Identification of CD24 as a marker for tumorigenesis of melanoma.OncoTargets and therapy · 2018Article
- The role of CCN4/WISP-1 in the cancerous phenotype.Cancer management and research · 2018Review
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells-derived fibroblasts (MSC-DF) constitute a significant portion of stromal fibroblasts in the tumor microenvironment (TME) and are key modulators of tumor progression. However, the molecular mechanisms that determine their tumor-regulatory function are poorly understood. Here, we uncover the Notch1 pathway as a molecular determinant that selectively controls the regulatory role of MSC-DF in melanoma metastasis. We demonstrate that the Notch1 pathway's activity is inversely correlated with the metastasis-regulating function of fibroblasts and can determine the metastasis-promoting or -suppressing phenotype of MSC-DF. When co-grafted with melanoma cells, MSC-DFNotch1-/- selectively promote, while MSC-DFN1IC+/+ preferentially suppress melanoma metastasis, but not growth, in mouse models. Consistently, conditioned media (CM) from MSC-DFNotch1-/- and MSC-DFN1IC+/+ oppositely, yet selectively regulates migration, but not growth of melanoma cells in vitro. Additionally, when co-cultured with metastatic melanoma cells in vitro, MSC-DFNotch1-/- support, while MSC-DFN1IC+/+ inhibit melanoma cells in the formation of spheroids. These findings expand the repertoire of Notch1 signaling as a molecular switch in determining the tumor metastasis-regulating function of MSC-DF. We also identified Wnt-induced secreted protein-1 (WISP-1) as a key downstream secretory mediator of Notch1 signaling to execute the influential role of MSC-DF on melanoma metastasis. These findings reveal the Notch1-WISP-1 axis as a crucial molecular determinant in governing stromal regulation of melanoma metastasis; thus, establishing this axis as a potential therapeutic target for melanoma metastasis.
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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.