ArticleOncotarget2012
Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.
Article in Oncotarget, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
- SIPA1 promotes epithelial-mesenchymal transition in colorectal cancer through STAT3 activation.Heliyon · 2024Article
- SIPA1 promotes angiogenesis by regulating VEGF secretion in Müller cells through STAT3 activation.Heliyon · 2024Article
- The Lipid Metabolism as Target and Modulator of BOLD-100 Anticancer Activity: Crosstalk with Histone Acetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Mesothelioma-associated fibroblasts enhance proliferation and migration of pleural mesothelioma cells via c-Met/PI3K and WNT signaling but do not protect against cisplatin.Journal of experimental & clinical cancer research : CR · 2023Article
- Fibroblast growth factor receptor 4 promotes glioblastoma progression: a central role of integrin-mediated cell invasiveness.Acta neuropathologica communications · 2022Article
- The Anticancer Ruthenium Compound BOLD-100 Targets Glycolysis and Generates a Metabolic Vulnerability towards Glucose Deprivation.Pharmaceutics · 2022Article
- Article
- SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis.Frontiers in cell and developmental biology · 2021Article
- Signatures of Discriminative Copy Number Aberrations in 31 Cancer Subtypes.Frontiers in genetics · 2021Article
- Inhibition of microRNA-300 inhibits cell adhesion, migration, and invasion of prostate cancer cells by promoting the expression ofCell cycle (Georgetown, Tex.) · 2020Article
- p53 Loss Mediates Hypersensitivity to ETS Transcription Factor Inhibition Based on PARylation-Mediated Cell Death Induction.Cancers · 2020Article
- The role of SIPA1 in the development of cancer and metastases (Review).Molecular and clinical oncology · 2020Review
- Lipid droplet-mediated scavenging as novel intrinsic and adaptive resistance factor against the multikinase inhibitor ponatinib.International journal of cancer · 2020Article
- TERT expression is susceptible to BRAF and ETS-factor inhibition in BRAFActa neuropathologica communications · 2019Article
- TNF-alpha and metalloproteases as key players in melanoma cells aggressiveness.Journal of experimental & clinical cancer research : CR · 2018Article
- Biological activity of PtScientific reports · 2018Article
- Altered membrane rigidity via enhanced endogenous cholesterol synthesis drives cancer cell resistance to destruxins.Oncotarget · 2018Article
- MMP-9 as a Candidate Marker of Response to BRAF Inhibitors in Melanoma Patients WithFrontiers in pharmacology · 2018Article
- CD44 drives aggressiveness and chemoresistance of a metastatic human osteosarcoma xenograft model.Oncotarget · 2017Article
- Therapeutic potential of bleomycin plus suicide or interferon-β gene transfer combination for spontaneous feline and canine melanoma.Oncoscience · 2017Article
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
Melanoma is a devastating skin cancer characterized by distinct biological subtypes. Besides frequent mutations in growth- and survival-promoting genes like BRAF and NRAS, melanomas additionally harbor complex non-random genomic alterations. Using an integrative approach, we have analysed genomic and gene expression changes in human melanoma cell lines (N=32) derived from primary tumors and various metastatic sites and investigated the relation to local growth aggressiveness as xenografts in immuno-compromised mice (N=22). Although the vast majority >90% of melanoma models harbored mutations in either BRAF or NRAS, significant differences in subcutaneous growth aggressiveness became obvious. Unsupervised clustering revealed that genomic alterations rather than gene expression data reflected this aggressive phenotype, while no association with histology, stage or metastatic site of the original melanoma was found. Genomic clustering allowed separation of melanoma models into two subgroups with differing local growth aggressiveness in vivo. Regarding genes expressed at significantly altered levels between these subgroups, a surprising correlation with the respective gene doses (>85% accordance) was found. Genes deregulated at the DNA and mRNA level included well-known cancer genes partly already linked to melanoma (RAS genes, PTEN, AURKA, MAPK inhibitors Sprouty/Spred), but also novel candidates like SIPA1 (a Rap1GAP). Pathway mining further supported deregulation of Rap1 signaling in the aggressive subgroup e.g. by additional repression of two Rap1GEFs. Accordingly, siRNA-mediated down-regulation of SIPA1 exerted significant effects on clonogenicity, adherence and migration in aggressive melanoma models. Together our data suggest that an aneuploidy-driven gene expression deregulation drives local aggressiveness in human melanoma.
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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.