First Author | Staebler S | Year | 2024 |
Journal | Cell Death Dis | Volume | 15 |
Issue | 5 | Pages | 351 |
PubMed ID | 38773108 | Mgi Jnum | J:348733 |
Mgi Id | MGI:7642338 | Doi | 10.1038/s41419-024-06733-3 |
Citation | Staebler S, et al. (2024) Transcription factor activating enhancer-binding protein 2epsilon (AP2epsilon) modulates phenotypic plasticity and progression of malignant melanoma. Cell Death Dis 15(5):351 |
abstractText | Malignant melanoma, the most aggressive form of skin cancer, is often incurable once metastatic dissemination of cancer cells to distant organs has occurred. We investigated the role of Transcription Factor Activating Enhancer-Binding Protein 2epsilon (AP2epsilon) in the progression of metastatic melanoma. Here, we observed that AP2epsilon is a potent activator of metastasis and newly revealed AP2epsilon to be an important player in melanoma plasticity. High levels of AP2epsilon lead to worsened prognosis of melanoma patients. Using a transgenic melanoma mouse model with a specific loss of AP2epsilon expression, we confirmed the impact of AP2epsilon to modulate the dynamic switch from a migratory to a proliferative phenotype. AP2epsilon deficient melanoma cells show a severely reduced migratory potential in vitro and reduced metastatic behavior in vivo. Consistently, we revealed increased activity of AP2epsilon in quiescent and migratory cells compared to heterogeneously proliferating cells in bioprinted 3D models. In conclusion, these findings disclose a yet-unknown role of AP2epsilon in maintaining plasticity and migration in malignant melanoma cells. |