ArticleThe Journal of experimental medicine2013
p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Survival expectations in melanoma patients: a molecular prognostic model associated with aging.Discover oncology · 2025Article
- PPP1R13L drives cervical cancer progression by suppressing p63-mediated PTEN transcription.Cellular and molecular life sciences : CMLS · 2025Article
- TRIM8: a double-edged sword in glioblastoma with the power to heal or hurt.Cellular & molecular biology letters · 2023Review
- p53 Family in Resistance to Targeted Therapy of Melanoma.International journal of molecular sciences · 2022Review
- Inhibition of USP28 overcomes Cisplatin-resistance of squamous tumors by suppression of the Fanconi anemia pathway.Cell death and differentiation · 2022Article
- A new ferroptosis-related genetic mutation risk model predicts the prognosis of skin cutaneous melanoma.Frontiers in genetics · 2022Article
- Article
- Melanoma Cell Intrinsic GABAInternational journal of radiation oncology, biology, physics · 2021Article
- Emerging Roles of TRIM8 in Health and Disease.Cells · 2021Review
- TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance.Biomedicines · 2021Review
- CD10 and p63 expression in a sarcomatoid undifferentiated melanoma: A cautionary (and molecularly annotated) tale.Journal of cutaneous pathology · 2020Article
- The Role of Epithelial-to-Mesenchymal Transition in Cutaneous Squamous Cell Carcinoma : Epithelial-to-Mesenchymal Transition in Cutaneous SCC.Current treatment options in oncology · 2020Review
- p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer.International journal of molecular sciences · 2019Review
- Expression profiles of p53/p73, NME and GLI families in metastatic melanoma tissue and cell lines.Scientific reports · 2019Article
- Metformin and 4SC-202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma.Cancer medicine · 2019Article
- Altered expression of p63 isoforms and expansion of p63- and club cell secretory protein-positive epithelial cells in the lung as novel features of aging.American journal of physiology. Cell physiology · 2019Article
- The Potential of Targeting P53 and HSP90 Overcoming Acquired MAPKi-Resistant Melanoma.Current treatment options in oncology · 2019Review
- Expression of Glut-1 in Malignant Melanoma and Melanocytic Nevi: an Immunohistochemical Study of 400 Cases.Pathology oncology research : POR · 2019Article
- TRIM8 Blunts the Pro-proliferative Action of ΔNp63α in a p53 Wild-Type Background.Frontiers in oncology · 2019Article
- Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterized. Mutations in TP53 occur infrequently, yet the TP53 apoptotic pathway is often abrogated. This may result from alterations in TP53 family members, including the TP53 homologue TP63. Here we demonstrate that TP63 has an antiapoptotic role in melanoma and is responsible for mediating chemoresistance. Although p63 was not expressed in primary melanocytes, up-regulation of p63 mRNA and protein was observed in melanoma cell lines and clinical samples, providing the first evidence of significant p63 expression in this lineage. Upon genotoxic stress, endogenous p63 isoforms were stabilized in both nuclear and mitochondrial subcellular compartments. Our data provide evidence of a physiological interaction between p63 with p53 whereby translocation of p63 to the mitochondria occurred through a codependent process with p53, whereas accumulation of p53 in the nucleus was prevented by p63. Using RNA interference technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance, revealing a novel oncogenic role for p63 in melanoma cells. Furthermore, expression of p63 in both primary and metastatic melanoma clinical samples significantly correlated with melanoma-specific deaths in these patients. Ultimately, these observations provide a possible explanation for abrogation of the p53-mediated apoptotic pathway in melanoma, implicating novel approaches aimed at sensitizing melanoma to therapeutic agents.
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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.