ArticlePigment cell & melanoma research2009
SKI knockdown inhibits human melanoma tumor growth in vivo.
Article in Pigment cell & melanoma research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- PAX3: A Driver of Normal Development and Disease.Biomolecules · 2026Review
- PAI-1 in Skin Malignancies: a Central Regulator of Tumor Progression and Therapeutic Resistance.Current treatment options in oncology · 2025Review
- The Essential Role of Angiogenesis in Adenosine 2A Receptor Deficiency-mediated Impairment of Wound Healing Involving c-Ski via the ERK/CREB Pathways.International journal of biological sciences · 2024Article
- Upregulation of proto-oncogene ski by thyroid hormone in the intestine and tail during Xenopus metamorphosis.General and comparative endocrinology · 2022Article
- Osteoarthritis-Related Inflammation Blocks TGF-β's Protective Effect on Chondrocyte Hypertrophy via (de)Phosphorylation of the SMAD2/3 Linker Region.International journal of molecular sciences · 2021Article
- Knockdown of Ski decreases osteosarcoma cell proliferation and migration by suppressing the PI3K/Akt signaling pathway.International journal of oncology · 2020Article
- Ski mediates TGF-β1-induced fibrosarcoma cell proliferation and promotes tumor growth.Journal of Cancer · 2020Article
- Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1.Nucleic acids research · 2018Article
- The role of DNA methylation in human trophoblast differentiation.Epigenetics · 2018Article
- Epigenetic profiling of ADHD symptoms trajectories: a prospective, methylome-wide study.Molecular psychiatry · 2017Article
- Ski modulate the characteristics of pancreatic cancer stem cells via regulating sonic hedgehog signaling pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Inhibiting Drivers of Non-mutational Drug Tolerance Is a Salvage Strategy for Targeted Melanoma Therapy.Cancer cell · 2016Article
- Epigenetic mechanisms involved in melanoma pathogenesis and chemoresistance.Annals of translational medicine · 2015Review
- TGF-β signal shifting between tumor suppression and fibro-carcinogenesis in human chronic liver diseases.Journal of gastroenterology · 2014Review
- Insights into the Transforming Growth Factor-β Signaling Pathway in Cutaneous Melanoma.Annals of dermatology · 2013Article
- SERPINE1 expression discriminates site-specific metastasis in human melanoma.Experimental dermatology · 2012Article
- Expression of microphthalmia-associated transcription factor (MITF), which is critical for melanoma progression, is inhibited by both transcription factor GLI2 and transforming growth factor-β.The Journal of biological chemistry · 2012Article
- Overexpression of SKI oncoprotein leads to p53 degradation through regulation of MDM2 protein sumoylation.The Journal of biological chemistry · 2012Article
- Non-canonical Smads phosphorylation induced by the glutamate release inhibitor, riluzole, through GSK3 activation in melanoma.PloS one · 2012Article
- Peroxisome proliferator-activated receptor γ (PPARγ) mediates a Ski oncogene-induced shift from glycolysis to oxidative energy metabolism.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The SKI protein represses the TGF-beta tumor suppressor pathway by associating with the Smad transcription factors. SKI is upregulated in human malignant melanoma tumors in a disease-progression manner and its overexpression promotes proliferation and migration of melanoma cells in vitro. The mechanisms by which SKI antagonizes TGF-beta signaling in vivo have not been fully elucidated. Here we show that human melanoma cells in which endogenous SKI expression was knocked down by RNAi produced minimal orthotopic tumor xenograft nodules that displayed low mitotic rate and prominent apoptosis. These minute tumors exhibited critical signatures of active TGF-beta signaling including high levels of nuclear Smad3 and p21(Waf-1), which are not found in the parental melanomas. To understand how SKI promotes tumor growth we used gain- and loss-of-function approaches and found that simultaneously to blocking the TGF-beta-growth inhibitory pathway, SKI promotes the switch of Smad3 from tumor suppression to oncogenesis by favoring phosphorylations of the Smad3 linker region in melanoma cells but not in normal human melanocytes. In this context, SKI is required for preventing TGF-beta-mediated downregulation of the oncogenic protein c-MYC, and for inducing the plasminogen activator inhibitor-1, a mediator of tumor growth and angiogenesis. Together, the results indicate that SKI exploits multiple regulatory levels of the TGF-beta pathway and its deficiency restores TGF-beta tumor suppressor and apoptotic activities in spite of the likely presence of oncogenic mutations in melanoma tumors.
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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.