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LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment

BACKGROUND: Malignant melanoma is a highly heterogeneous skin cancer with the highest mortality rate among dermatological cancers. Catenins form functional networks in the nucleus to regulate gene expression and determine cell fate. Dysregulation of catenin expression correlates with the malignant c...

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Autores principales: Hu, Yi-dou, Wu, Ke, Liu, Yuan-jie, Zhang, Qian, Shen, Hui, Ji, Jin, Fang, Dong, Xi, Song-yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623712/
https://www.ncbi.nlm.nih.gov/pubmed/37924160
http://dx.doi.org/10.1186/s13062-023-00424-3
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author Hu, Yi-dou
Wu, Ke
Liu, Yuan-jie
Zhang, Qian
Shen, Hui
Ji, Jin
Fang, Dong
Xi, Song-yang
author_facet Hu, Yi-dou
Wu, Ke
Liu, Yuan-jie
Zhang, Qian
Shen, Hui
Ji, Jin
Fang, Dong
Xi, Song-yang
author_sort Hu, Yi-dou
collection PubMed
description BACKGROUND: Malignant melanoma is a highly heterogeneous skin cancer with the highest mortality rate among dermatological cancers. Catenins form functional networks in the nucleus to regulate gene expression and determine cell fate. Dysregulation of catenin expression correlates with the malignant characteristics of the tumor. We aimed to investigate the regulatory mechanisms of catenins in melanoma and to further define the function of catenin-related molecular signaling in the tumor microenvironment. METHODS: In this study, a bioinformatics approach combined with experimental validation was used to explore the potential tumor biology mechanisms of catenin-related signaling. RESULTS: Melanoma patients can be divided into two catenin clusters. Patients defined by high Junction Plakoglobin (JUP), Plakophilin 1 (PKP1), Plakophilin 3 (PKP3) levels (C2) had shorter survival time than other patients (C1). We demonstrated that JUP regulates Anterior Gradient 2 (AGR2)/LY6/PLAUR Domain Containing 3 (LYPD3) to maintain melanoma stemness and promotes glycolysis. We also found that LYPD3 was co-expressed with S100A9 and associated with immunosuppressive tumor microenvironment (TME). CONCLUSION: The JUP/AGR2/LYPD3 signaling axis plays an important role in the malignant features of melanoma. Targeting the JUP/AGR2/LYPD3 signaling axis can help develop promising drugs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00424-3.
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spelling pubmed-106237122023-11-04 LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment Hu, Yi-dou Wu, Ke Liu, Yuan-jie Zhang, Qian Shen, Hui Ji, Jin Fang, Dong Xi, Song-yang Biol Direct Research BACKGROUND: Malignant melanoma is a highly heterogeneous skin cancer with the highest mortality rate among dermatological cancers. Catenins form functional networks in the nucleus to regulate gene expression and determine cell fate. Dysregulation of catenin expression correlates with the malignant characteristics of the tumor. We aimed to investigate the regulatory mechanisms of catenins in melanoma and to further define the function of catenin-related molecular signaling in the tumor microenvironment. METHODS: In this study, a bioinformatics approach combined with experimental validation was used to explore the potential tumor biology mechanisms of catenin-related signaling. RESULTS: Melanoma patients can be divided into two catenin clusters. Patients defined by high Junction Plakoglobin (JUP), Plakophilin 1 (PKP1), Plakophilin 3 (PKP3) levels (C2) had shorter survival time than other patients (C1). We demonstrated that JUP regulates Anterior Gradient 2 (AGR2)/LY6/PLAUR Domain Containing 3 (LYPD3) to maintain melanoma stemness and promotes glycolysis. We also found that LYPD3 was co-expressed with S100A9 and associated with immunosuppressive tumor microenvironment (TME). CONCLUSION: The JUP/AGR2/LYPD3 signaling axis plays an important role in the malignant features of melanoma. Targeting the JUP/AGR2/LYPD3 signaling axis can help develop promising drugs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00424-3. BioMed Central 2023-11-03 /pmc/articles/PMC10623712/ /pubmed/37924160 http://dx.doi.org/10.1186/s13062-023-00424-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Hu, Yi-dou
Wu, Ke
Liu, Yuan-jie
Zhang, Qian
Shen, Hui
Ji, Jin
Fang, Dong
Xi, Song-yang
LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment
title LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment
title_full LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment
title_fullStr LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment
title_full_unstemmed LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment
title_short LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment
title_sort ly6/plaur domain containing 3 (lypd3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623712/
https://www.ncbi.nlm.nih.gov/pubmed/37924160
http://dx.doi.org/10.1186/s13062-023-00424-3
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