ArticleNeoplasia (New York, N.Y.)2014
Harnessing the p53-PUMA axis to overcome DNA damage resistance in renal cell carcinoma.
Article in Neoplasia (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- PUMA reduces FASN ubiquitination to promote lipid accumulation and tumor progression in human clear cell renal cell carcinoma.Cell death & disease · 2025Article
- Bluetongue Viruses Act as Novel Oncolytic Viruses to Effectively Inhibit Human Renal Cancer Cell Growth In Vitro and In Vivo.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Characterization of Histone Deacetylase Mechanisms in Cancer Development.Frontiers in oncology · 2021Review
- Inhibition of miR-34a-5p can rescue disruption of the p53-DAPK axis to suppress progression of clear cell renal cell carcinoma.Molecular oncology · 2019Article
- Sensitization of Resistance Ovarian Cancer Cells to Cisplatin by Biogenic Synthesized Silver Nanoparticles through p53 Activation.Iranian journal of pharmaceutical research : IJPR · 2019Article
- Expression and clinical significance of ATM and PUMA gene in patients with colorectal cancer.Oncology letters · 2017Article
- MiR-204 enhances mitochondrial apoptosis in doxorubicin-treated prostate cancer cells by targeting SIRT1/p53 pathway.Oncotarget · 2017Article
- SHARPIN Facilitates p53 Degradation in Breast Cancer Cells.Neoplasia (New York, N.Y.) · 2017Article
- Curcumin enhances temsirolimus-induced apoptosis in human renal carcinoma cells through upregulation of YAP/p53.Oncology letters · 2016Article
- HDACs and HDAC Inhibitors in Cancer Development and Therapy.Cold Spring Harbor perspectives in medicine · 2016Review
- Decreased Expression of SRSF2 Splicing Factor Inhibits Apoptotic Pathways in Renal Cancer.International journal of molecular sciences · 2016Article
- Functional Studies on Primary Tubular Epithelial Cells Indicate a Tumor Suppressor Role of SETD2 in Clear Cell Renal Cell Carcinoma.Neoplasia (New York, N.Y.) · 2016Article
- Uncoupling of PUMA Expression and Apoptosis Contributes to Functional Heterogeneity in Renal Cell Carcinoma - Prognostic and Translational Implications.Translational oncology · 2015Article
- The Dysregulation of Lysine Acetylation in Esophageal Squamous Cell Carcinoma: Mechanisms, Therapeutic Targets and Clinical Perspectives.Technology in cancer research & treatmentReview
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to DNA damage-induced apoptosis is a hallmark of cancer and a major cause of treatment failure and lethal disease outcome. A tumor entity that is largely resistant to DNA-damaging therapies including chemo- or radiotherapy is renal cell carcinoma (RCC). This study was designed to explore the underlying molecular mechanisms of DNA damage resistance in RCC to develop strategies to resensitize tumor cells to DNA damage-induced apoptosis. Here, we show that apoptosis-resistant RCC cells have a disconnect between activation of p53 and upregulation of the downstream proapoptotic protein p53 upregulated modulator of apoptosis (PUMA). We demonstrate that this disconnect is not caused by gene-specific repression through CCCTC-binding factor (CTCF) but instead by aberrant chromatin compaction. Treatment with an HDAC inhibitor was found to effectively reactivate PUMA expression on the mRNA and protein level and to revert resistance to DNA damage-induced cell death. Ectopic expression of PUMA was found to resensitize a panel of RCC cell lines to four different DNA-damaging agents tested. Remarkably, all RCC cell lines analyzed were wild-type for p53, and a knockdown was likewise able to sensitize RCC cells to acute genotoxic stress. Taken together, our results indicate that DNA damage resistance in RCC is reversible, involves the p53-PUMA axis, and is potentially targetable to improve the oncological outcomes of RCC patients.
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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.