ArticleThe Journal of clinical investigation2019
SMAD signaling promotes melanoma metastasis independently of phenotype switching.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- Emerging role of ARHGAP29 in melanoma cell phenotype switching.Molecular oncology · 2026Article
- Modeling rare melanoma subtypes: mechanisms, microenvironments and translational opportunities.Frontiers in oncology · 2026Review
- Gene-expression signature predicts autoimmune toxicity in metastatic melanoma.Journal for immunotherapy of cancer · 2025Article
- Exploring the relation between TGF-β pathway activity and response to checkpoint inhibition in patients with metastatic melanoma.Clinical and experimental immunology · 2025Article
- Role of exosomes in transforming growth factor-β-mediated cancer cell plasticity and drug resistance.Exploration of targeted anti-tumor therapy · 2025Review
- TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.Cell death & disease · 2024Article
- Kinesin Family Member-18A (KIF18A) Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma.Digestive diseases and sciences · 2024Article
- Long non-coding RNA GRASLND links melanoma differentiation and interferon-gamma response.Frontiers in molecular biosciences · 2024Article
- The crucial roles of mGenes & diseases · 2023Review
- The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential.EMBO reports · 2023Article
- Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance.International journal of molecular sciences · 2023Review
- Inhibition of anti-tumor immunity by melanoma cell-derived Activin-A depends on STING.Frontiers in immunology · 2023Article
- EZH2-triggered methylation of SMAD3 promotes its activation and tumor metastasis.The Journal of clinical investigation · 2022Article
- Hierarchy of TGFβ/SMAD, Hippo/YAP/TAZ, and Wnt/β-catenin signaling in melanoma phenotype switching.Life science alliance · 2022Article
- A score of DNA damage repair pathway with the predictive ability for chemotherapy and immunotherapy is strongly associated with immune signaling pathway in pan-cancer.Frontiers in immunology · 2022Article
- Loss of YY1, a Regulator of Metabolism in Melanoma, Drives Melanoma Cell Invasiveness and Metastasis Formation.Frontiers in cell and developmental biology · 2022Article
- Genomic and Transcriptomic Underpinnings of Melanoma Genesis, Progression, and Metastasis.Cancers · 2021Review
- Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation.Developmental cell · 2021Article
- Progression of melanoma is suppressed by targeting all transforming growth factor‑β isoforms with an Fc chimeric receptor.Oncology reports · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of metastatic melanoma is thought to require the dynamic shifting of neoplastic cells between proliferative and invasive phenotypes. Contrary to this conventional "phenotype switching" model, we now show that disease progression can involve malignant melanoma cells simultaneously displaying proliferative and invasive properties. Using a genetic mouse model of melanoma in combination with in vitro analyses of melanoma cell lines, we found that conditional deletion of the downstream signaling molecule Smad4, which abrogates all canonical TGF-β signaling, indeed inhibits both tumor growth and metastasis. Conditional deletion of the inhibitory signaling factor Smad7, however, generated cells that are both highly invasive and proliferative, indicating that invasiveness is compatible with a high proliferation rate. In fact, conditional Smad7 deletion led to sustained melanoma growth and at the same time promoted massive metastasis formation, a result consistent with data indicating that low SMAD7 levels in patient tumors are associated with a poor survival. Our findings reveal that modulation of SMAD7 levels can overcome the need for phenotype switching during tumor progression and may thus represent a novel therapeutic target in metastatic disease.
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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.