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SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle
MCT1 is a critical protein found in monocarboxylate transporters that plays a significant role in regulating the lactate shuttle. However, the post‐transcriptional modifications that regulate MCT1 are not clearly identified. In this study, it is reported that SETDB1 interacts with MCT1, leading to i...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558670/ https://www.ncbi.nlm.nih.gov/pubmed/37541664 http://dx.doi.org/10.1002/advs.202301871 |
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author | She, Xiaowei Wu, Qi Rao, Zejun Song, Da Huang, Changsheng Feng, Shengjie Liu, Anyi Liu, Lang Wan, Kairui Li, Xun Yu, Chengxin Qiu, Cheng Luo, Xuelai Hu, Junbo Wang, Guihua Xu, Feng Sun, Li |
author_facet | She, Xiaowei Wu, Qi Rao, Zejun Song, Da Huang, Changsheng Feng, Shengjie Liu, Anyi Liu, Lang Wan, Kairui Li, Xun Yu, Chengxin Qiu, Cheng Luo, Xuelai Hu, Junbo Wang, Guihua Xu, Feng Sun, Li |
author_sort | She, Xiaowei |
collection | PubMed |
description | MCT1 is a critical protein found in monocarboxylate transporters that plays a significant role in regulating the lactate shuttle. However, the post‐transcriptional modifications that regulate MCT1 are not clearly identified. In this study, it is reported that SETDB1 interacts with MCT1, leading to its stabilization. These findings reveal a novel post‐translational modification of MCT1, in which SETDB1 methylation occurs at K473 in vitro and in vivo. This methylation inhibits the interaction between MCT1 and Tollip, which blocks Tollip‐mediated autophagic degradation of MCT1. Furthermore, MCT1 K473 tri‐methylation promotes tumor glycolysis and M2‐like polarization of tumor‐associated macrophages in colorectal cancer (CRC), which enhances the lactate shuttle. In clinical studies, MCT1 K473 tri‐methylation is found to be upregulated and positively correlated with tumor progression and overall survival in CRC. This discovery suggests that SETDB1‐mediated tri‐methylation at K473 is a vital regulatory mechanism for lactate shuttle and tumor progression. Additionally, MCT1 K473 methylation may be a potential prognostic biomarker and promising therapeutic target for CRC. |
format | Online Article Text |
id | pubmed-10558670 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105586702023-10-08 SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle She, Xiaowei Wu, Qi Rao, Zejun Song, Da Huang, Changsheng Feng, Shengjie Liu, Anyi Liu, Lang Wan, Kairui Li, Xun Yu, Chengxin Qiu, Cheng Luo, Xuelai Hu, Junbo Wang, Guihua Xu, Feng Sun, Li Adv Sci (Weinh) Research Articles MCT1 is a critical protein found in monocarboxylate transporters that plays a significant role in regulating the lactate shuttle. However, the post‐transcriptional modifications that regulate MCT1 are not clearly identified. In this study, it is reported that SETDB1 interacts with MCT1, leading to its stabilization. These findings reveal a novel post‐translational modification of MCT1, in which SETDB1 methylation occurs at K473 in vitro and in vivo. This methylation inhibits the interaction between MCT1 and Tollip, which blocks Tollip‐mediated autophagic degradation of MCT1. Furthermore, MCT1 K473 tri‐methylation promotes tumor glycolysis and M2‐like polarization of tumor‐associated macrophages in colorectal cancer (CRC), which enhances the lactate shuttle. In clinical studies, MCT1 K473 tri‐methylation is found to be upregulated and positively correlated with tumor progression and overall survival in CRC. This discovery suggests that SETDB1‐mediated tri‐methylation at K473 is a vital regulatory mechanism for lactate shuttle and tumor progression. Additionally, MCT1 K473 methylation may be a potential prognostic biomarker and promising therapeutic target for CRC. John Wiley and Sons Inc. 2023-08-04 /pmc/articles/PMC10558670/ /pubmed/37541664 http://dx.doi.org/10.1002/advs.202301871 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles She, Xiaowei Wu, Qi Rao, Zejun Song, Da Huang, Changsheng Feng, Shengjie Liu, Anyi Liu, Lang Wan, Kairui Li, Xun Yu, Chengxin Qiu, Cheng Luo, Xuelai Hu, Junbo Wang, Guihua Xu, Feng Sun, Li SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle |
title | SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle |
title_full | SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle |
title_fullStr | SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle |
title_full_unstemmed | SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle |
title_short | SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle |
title_sort | setdb1 methylates mct1 promoting tumor progression by enhancing the lactate shuttle |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558670/ https://www.ncbi.nlm.nih.gov/pubmed/37541664 http://dx.doi.org/10.1002/advs.202301871 |
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