| Autor: |
Nyberg, William A, Velasquez‐Pulgarin, Diego A, He, Tianlin, Sjöstrand, Maria, Pellé, Lucia, Covacu, Ruxandra, Espinosa, Alexander |
| Zdroj: |
EMBO Reports; 1/9/2023, Vol. 24 Issue 1, p1-12, 12p |
| Abstrakt: |
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. Synopsis: TRIM28 controls JUNB transcription that in turn induces RAS signature genes and suppresses YAP1 signature genes. TRIM28 depletion therefore leads to higher JUNB expression followed by increased melanoma growth and decreased melanoma invasiveness. TRIM28 is highly expressed in aggressive melanoma tumors.TRIM28 negatively regulates the transcriptional elongation of JUNB.JUNB expression induces a switch from melanoma invasiveness to melanoma growth. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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