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YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance

Malignant melanoma, with its increasing incidence and high potential to form metastases, is one of the most aggressive types of skin malignancies responsible for a significant number of deaths worldwide. However, melanoma also demonstrates a high potential for induction of a specific adaptive anti-t...

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Autores principales: Kwiatkowska, Dominika, Mazur, Ewelina, Reich, Adam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198644/
https://www.ncbi.nlm.nih.gov/pubmed/35719931
http://dx.doi.org/10.3389/fonc.2022.856963
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author Kwiatkowska, Dominika
Mazur, Ewelina
Reich, Adam
author_facet Kwiatkowska, Dominika
Mazur, Ewelina
Reich, Adam
author_sort Kwiatkowska, Dominika
collection PubMed
description Malignant melanoma, with its increasing incidence and high potential to form metastases, is one of the most aggressive types of skin malignancies responsible for a significant number of deaths worldwide. However, melanoma also demonstrates a high potential for induction of a specific adaptive anti-tumor immune response being one of the most immunogenic malignancies. Yin Yang 1 (YY1) transcription factor is essential to numerous cellular processes and the regulation of transcriptional and posttranslational modifications of various genes. It regulates programmed cell death 1 (PD1) and lymphocyte-activation gene 3 (LAG3) by binding to its promoters, as well as suppresses both Fas and TRAIL by negatively regulating DR5 transcription and expression and interaction with the silencer region of the Fas promoter, rendering cells resistant to apoptosis. Moreover, YY1 is considered a master regulator in various stages of embryogenesis, especially in neural crest stem cells (NCSCs) survival and proliferation as it acts as transcriptional repressor on cancer stem cells-related transcription factors. In addition, YY1 increases the metastatic potential of melanoma through negative regulation of microRNA-9 (miR-9) expression, acts as a cofactor of transcription factor EB (TFEB) and contributes to autophagy regulation, mainly due to increased transcription of genes related to autophagy and lysosome biogenesis. Therefore, focusing on the detailed biology and administration of therapies that directly target YY1 or crosstalk pathways in malignant melanoma could facilitate the development of new and more effective treatment strategies and improve patients’ outcomes.
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spelling pubmed-91986442022-06-16 YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance Kwiatkowska, Dominika Mazur, Ewelina Reich, Adam Front Oncol Oncology Malignant melanoma, with its increasing incidence and high potential to form metastases, is one of the most aggressive types of skin malignancies responsible for a significant number of deaths worldwide. However, melanoma also demonstrates a high potential for induction of a specific adaptive anti-tumor immune response being one of the most immunogenic malignancies. Yin Yang 1 (YY1) transcription factor is essential to numerous cellular processes and the regulation of transcriptional and posttranslational modifications of various genes. It regulates programmed cell death 1 (PD1) and lymphocyte-activation gene 3 (LAG3) by binding to its promoters, as well as suppresses both Fas and TRAIL by negatively regulating DR5 transcription and expression and interaction with the silencer region of the Fas promoter, rendering cells resistant to apoptosis. Moreover, YY1 is considered a master regulator in various stages of embryogenesis, especially in neural crest stem cells (NCSCs) survival and proliferation as it acts as transcriptional repressor on cancer stem cells-related transcription factors. In addition, YY1 increases the metastatic potential of melanoma through negative regulation of microRNA-9 (miR-9) expression, acts as a cofactor of transcription factor EB (TFEB) and contributes to autophagy regulation, mainly due to increased transcription of genes related to autophagy and lysosome biogenesis. Therefore, focusing on the detailed biology and administration of therapies that directly target YY1 or crosstalk pathways in malignant melanoma could facilitate the development of new and more effective treatment strategies and improve patients’ outcomes. Frontiers Media S.A. 2022-06-01 /pmc/articles/PMC9198644/ /pubmed/35719931 http://dx.doi.org/10.3389/fonc.2022.856963 Text en Copyright © 2022 Kwiatkowska, Mazur and Reich https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Kwiatkowska, Dominika
Mazur, Ewelina
Reich, Adam
YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance
title YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance
title_full YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance
title_fullStr YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance
title_full_unstemmed YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance
title_short YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance
title_sort yy1 is a key player in melanoma immunotherapy/targeted treatment resistance
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198644/
https://www.ncbi.nlm.nih.gov/pubmed/35719931
http://dx.doi.org/10.3389/fonc.2022.856963
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