The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
MITF and c-Jun antagonism interconnects melanoma dedifferentiation with pro-inflammatory cytokine responsiveness and myeloid cell recruitment
Open accessAbstract
Inflammation promotes phenotypic plasticity in melanoma, a source of non-genetic heterogeneity, but the molecular framework is poorly understood. Here we use functional genomic approaches and identify a reciprocal antagonism between the melanocyte lineage transcription factor MITF and c-Jun, which interconnects inflammation-induced dedifferentiation with pro-inflammatory cytokine responsiveness of melanoma cells favouring myeloid cell recruitment. We show that pro-inflammatory cytokines such as TNF-α instigate gradual suppression of MITF expression through c-Jun. MITF itself binds to the c-Jun regulatory genomic region and its reduction increases c-Jun expression that in turn amplifies TNF-stimulated cytokine expression with further MITF suppression. This feed-forward mechanism turns poor peak-like transcriptional responses to TNF-α into progressive and persistent cytokine and chemokine induction. Consistently, inflammatory MITF low/c-Jun high syngeneic mouse melanomas recruit myeloid immune cells into the tumour microenvironment as recapitulated by their human counterparts. Our study suggests myeloid cell-directed therapies may be useful for MITF low/c-Jun high melanomas to counteract their growth-promoting and immunosuppressive functions.
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PD-1 blockade induces responses by inhibiting adaptive immune resistance
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Nivolumab in Previously Untreated Melanoma without BRAF Mutation
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Genomic classification of cutaneous melanoma
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Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity
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A landscape of driver mutations in melanoma
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Cited by
Tsoi, J., Robert, L., Paraiso, K., Galvan, C., Sheu, K. M., Lay, J., Wong, D. J. L., Atefi, M., Shirazi, R., Wang, X., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.017 · Cited by 938
Goding, C. R., & Arnheiter, H. (2019) · Genes & Development · doi:10.1101/gad.324657.119 · Cited by 430
Self-citationPhenotype plasticity as enabler of melanoma progression and therapy resistance
Arozarena, I., & Wellbrock, C. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0154-4 · Cited by 381
The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology
Kawakami, A., & Fisher, D. E. (2017) · Laboratory Investigation · doi:10.1038/labinvest.2017.9 · Cited by 326
Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities
Rambow, F., Marine, J.-C., & Goding, C. R. (2019) · Genes & Development · doi:10.1101/gad.329771.119 · Cited by 325
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Metadata
- Authors
- Riesenberg, S., Groetchen, A., Siddaway, R., Bald, T., Reinhardt, J., Smorra, D., Kohlmeyer, J., Renn, M., Phung, B., Aymans, P., Schmidt, T., Hornung, V., Davidson, I., Goding, C. R., Jönsson, G., Landsberg, J., Tüting, T., & Hölzel, M.
- Venue
- Nature Communications
- Published
- 2015-11-04
- Volume
- 6
- Issue
- 1
- Pages
- 8755-8755
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2186855780
- Cited by
- 227
- References
- 24
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- gold
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- Riesenberg, S., Groetchen, A., Siddaway, R., Bald, T., Reinhardt, J., Smorra, D., Kohlmeyer, J., Renn, M., Phung, B., Aymans, P., Schmidt, T., Hornung, V., Davidson, I., Goding, C. R., Jönsson, G., Landsberg, J., Tüting, T., & Hölzel, M. (2015). MITF and c-Jun antagonism interconnects melanoma dedifferentiation with pro-inflammatory cytokine responsiveness and myeloid cell recruitment. Nature Communications. https://doi.org/10.1038/ncomms9755
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