ArticleOncogene2011
SPARC functions as an anti-stress factor by inactivating p53 through Akt-mediated MDM2 phosphorylation to promote melanoma cell survival.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 77 citations in OpenAlex.
- Tumor antigen PRAME promotes melanoma growth by inactivating p53 through the SIRT1-DBC1 axis.Oncogene · 2025Article
- Regulatory Mechanisms of SPARC Overexpression in Melanoma Progression.International journal of molecular sciences · 2025Article
- SPARC: a potential target for functional nanomaterials and drugs.Frontiers in molecular biosciences · 2023Review
- Ageing of skeletal muscle extracellular matrix and mitochondria: finding a potential link.Annals of medicine · 2023Review
- Mouse fetal growth restriction through parental and fetal immune gene variation and intercellular communications cascade.Nature communications · 2022Article
- Article
- Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo.Journal of experimental & clinical cancer research : CR · 2021Article
- A 9-kDa matricellular SPARC fragment released by cathepsin D exhibits pro-tumor activity in the triple-negative breast cancer microenvironment.Theranostics · 2021Article
- Melanoma stem cell maintenance and chemo-resistance are mediated by CD133 signal to PI3K-dependent pathways.Oncogene · 2020Article
- PRKAA1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells Through Activating JNK1 and Akt Pathways.Oncology research · 2020Article
- Salinomycin and Sulforaphane Exerted Synergistic Antiproliferative and Proapoptotic Effects on Colorectal Cancer Cells by Inhibiting the PI3K/Akt Signaling Pathway in vitro and in vivo.OncoTargets and therapy · 2020Article
- Overview of MDM2 and B-RAF Expression in Gastric Lesions.Open access Macedonian journal of medical sciences · 2018Article
- Article
- Biomacromolecules as carriers in drug delivery and tissue engineering.Acta pharmaceutica Sinica. B · 2018Review
- Protein-Protein Interaction Network Analysis for a Biomarker Panel Related to Human Esophageal AdenocarcinomaAsian Pacific journal of cancer prevention : APJCP · 2017Article
- Cariporide Enhances the DNA Damage and Apoptosis in Acid-tolerable Malignant Mesothelioma H-2452 Cells.Molecules and cells · 2017Article
- Mechanism of melanoma cells selective apoptosis induced by a photoactive NADPH analogue.Oncotarget · 2016Article
- p53, a potential predictor of Helicobacter pylori infection-associated gastric carcinogenesis?Oncotarget · 2016Review
- Low-dose radiation prevents type 1 diabetes-induced cardiomyopathy via activation of AKT mediated anti-apoptotic and anti-oxidant effects.Journal of cellular and molecular medicine · 2016Article
- Loss of Sparc in p53-null Astrocytes Promotes Macrophage Activation and Phagocytosis Resulting in Decreased Tumor Size and Tumor Cell Survival.Brain pathology (Zurich, Switzerland) · 2015Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant expression of Secreted Protein Acidic and Rich in Cysteine (SPARC)/osteonectin has been associated with an invasive tumor cell phenotype and poor outcome in human melanomas. Although it is known that SPARC controls melanoma tumorigenesis, the precise role of SPARC in melanoma cell survival is still unclear. Here, we show that SPARC has a cell-autonomous survival activity, which requires Akt-dependent regulation of p53. Suppression of SPARC by RNA interference in several human melanoma cells and xenografted A375 tumors triggers apoptotic cell death through the mitochondrial intrinsic pathway and activation of caspase-3. Cell death induced by depletion of SPARC is dependent on p53 and induction of Bax, and results in the generation of ROS. Stabilization of p53 in SPARC-depleted cells is associated with a decrease in Akt-mediated activating phosphorylation of MDM2. Inhibition of Akt signaling pathway is important for the observed changes as overexpression of constitutively active Akt protects cells against apoptosis induced by SPARC depletion. Conversely, increased expression of SPARC stimulates Akt and MDM2 phosphorylation, thus facilitating p53 degradation. Finally, we show that overexpression of SPARC renders cells more resistant to the p53-mediated cytotoxic effects of the DNA-damaging drug actinomycin-D. Our study indicates that SPARC functions through activation of Akt and MDM2 to limit p53 levels and that acquired expression of SPARC during melanoma development would confer survival advantages through suppression of p53-dependent apoptotic pathways.
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