The bromodomain protein TRIM28 controls the balance between growth and invasiveness in melanoma

Abstract: Melanoma tumors are highly metastatic partly due to the ability of melanoma cells to transition between invasive and proliferative states. However, the mechanisms underlying this plasticity are still not fully understood. To identify new epigenetic regulators of melanoma plasticity, we combined data mining, tumor models, proximity proteomics, and CUT&RUN sequencing. We focus on the druggable family of bromodomain epigenetic readers and identify TRIM28 as a new regulator of melanoma plasticity. We find that TRIM28 promotes the expression of pro‐invasive genes and that TRIM28 controls the balance between invasiveness and growth of melanoma cells. We demonstrate that TRIM28 acts via the transcription factor JUNB that directly regulates the expression of pro‐invasive and pro‐growth genes. Mechanistically, TRIM28 controls the expression of JUNB by negatively regulating its transcriptional elongation by RNA polymerase II. In conclusion, our results demonstrate that a TRIM28–JUNB axis controls the balance between invasiveness and growth in melanoma tumors and suggest that the bromodomain protein TRIM28 could be targeted to reduce tumor spread.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
The bromodomain protein TRIM28 controls the balance between growth and invasiveness in melanoma ; day:07 ; month:11 ; year:2022 ; extent:18
EMBO reports / European Molecular Biology Organization ; (07.11.2022) (gesamt 18)

Creator
Nyberg, William A.
Velasquez‐Pulgarin, Diego A.
He, Tianlin
Sjöstrand, Maria
Pellé, Lucia
Covacu, Ruxandra
Espinosa, Alexander

DOI
10.15252/embr.202254944
URN
urn:nbn:de:101:1-2022110714144306021591
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:31 AM CEST

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Associated

  • Nyberg, William A.
  • Velasquez‐Pulgarin, Diego A.
  • He, Tianlin
  • Sjöstrand, Maria
  • Pellé, Lucia
  • Covacu, Ruxandra
  • Espinosa, Alexander

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