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p53 Promotes Cytokine Expression in Melanoma to Regulate Drug Resistance and Migration
Abstract
The transcription factor p53 is frequently lost during tumor development in solid tumors; however, most melanomas retain a wild type p53 protein. The presence of wild type p53 in melanoma has fueled speculation that p53 may play a neutral or pro-tumorigenic role in this disease. Here we show that p53 is functional in human melanoma cell lines, and that loss of p53 results in a general reduction in basal NF-kB regulated cytokine production. The reduced cytokine expression triggered by p53 loss is broad and includes key inflammatory chemokines, such as CXCL1, CXCL8, and the IL6 class cytokine LIF, resulting in a reduced ability to induce chemotactic-dependent migration of tumor cells and immune cells and increased sensitivity to BRAF inhibition. Taken together, this result indicates that wild type p53 regulates cytokine expression and induces cytokine-dependent phenotype on melanoma.
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“Further, TP53 is an essential regulator for cytokine expression in tumor cells 38-40, actively reshaping the profile of cytokines and chemokines secreted by cancer cells in vitro and in vivo.”
From Combined Point Mutation in a Single Allele of the TP53 Gene Potentiates the Oncogenic and Transcriptional Properties of TP53 in Lung Cancer (2026) · cites this paper as [38]
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Cited by
Bian, S., Bian, H., Koyama, H., Kompaniiets, D., Tse, W., Shah, M. V., Al-Kali, A., Miron, A., Liu, B., & Liu, S. (2026) · International Journal of Biological Sciences · doi:10.7150/ijbs.131687
Metadata
- Authors
- Pandya, P., Kublo, L., & Stewart-Ornstein, J.
- Affiliations
- Department of Computational and System Biology, Hillman Cancer Center & University of Pittsburgh, Pittsburgh, PA 15232, USA
- ORCID
- Pandya, Pinakin
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2022-01-25
- Volume
- 11
- Issue
- 3
- Pages
- 405
- ISSN
- 2073-4409
- Cited by
- 18
- References
- 5
- Language
- en
- Funders
- National Cancer Institute (CA207727-04)
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