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SUMOylated MAFB promotes colorectal cancer tumorigenesis

The transcription factor, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), promotes tumorigenesis in some cancers. In this study, we found that MAFB levels were increased in clinical colorectal cancer (CRC) samples, and higher expression correlated with more advanced TNM stage....

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Autores principales: Yang, Lin-Sen, Zhang, Xiao-Jian, Xie, Yin-Yin, Sun, Xiao-Jian, Zhao, Ren, Huang, Qiu-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347783/
https://www.ncbi.nlm.nih.gov/pubmed/27829226
http://dx.doi.org/10.18632/oncotarget.13129
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author Yang, Lin-Sen
Zhang, Xiao-Jian
Xie, Yin-Yin
Sun, Xiao-Jian
Zhao, Ren
Huang, Qiu-Hua
author_facet Yang, Lin-Sen
Zhang, Xiao-Jian
Xie, Yin-Yin
Sun, Xiao-Jian
Zhao, Ren
Huang, Qiu-Hua
author_sort Yang, Lin-Sen
collection PubMed
description The transcription factor, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), promotes tumorigenesis in some cancers. In this study, we found that MAFB levels were increased in clinical colorectal cancer (CRC) samples, and higher expression correlated with more advanced TNM stage. We identified MAFB amplifications in a majority of tumor types in an assessment of The Cancer Genome Atlas database. Altered MAFB levels due to gene amplification, deletion, mutation, or transcription upregulation occurred in 9% of CRC cases within the database. shRNA knockdown experiments demonstrated that MAFB deficiency blocked CRC cell proliferation by arresting the cell cycle at G0/G1 phase in vitro. We found that MAFB could be SUMOylated by SUMO1 at lysine 32, and this modification was critical for cell cycle regulation by MAFB in CRC cells. SUMOylated MAFB directly regulated cyclin-dependent kinase 6 transcription by binding to its promoter. MAFB knockdown CRC cell xenograft tumors in mice grew more slowly than controls, and wild-type MAFB-overexpressing tumors grew more quickly than tumors overexpressing MAFB mutated at lysine 32. These data suggest that SUMOylated MAFB promotes CRC tumorigenesis through cell cycle regulation. MAFB and its SUMOylation process may serve as novel therapeutic targets for CRC treatment.
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spelling pubmed-53477832017-03-31 SUMOylated MAFB promotes colorectal cancer tumorigenesis Yang, Lin-Sen Zhang, Xiao-Jian Xie, Yin-Yin Sun, Xiao-Jian Zhao, Ren Huang, Qiu-Hua Oncotarget Research Paper The transcription factor, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), promotes tumorigenesis in some cancers. In this study, we found that MAFB levels were increased in clinical colorectal cancer (CRC) samples, and higher expression correlated with more advanced TNM stage. We identified MAFB amplifications in a majority of tumor types in an assessment of The Cancer Genome Atlas database. Altered MAFB levels due to gene amplification, deletion, mutation, or transcription upregulation occurred in 9% of CRC cases within the database. shRNA knockdown experiments demonstrated that MAFB deficiency blocked CRC cell proliferation by arresting the cell cycle at G0/G1 phase in vitro. We found that MAFB could be SUMOylated by SUMO1 at lysine 32, and this modification was critical for cell cycle regulation by MAFB in CRC cells. SUMOylated MAFB directly regulated cyclin-dependent kinase 6 transcription by binding to its promoter. MAFB knockdown CRC cell xenograft tumors in mice grew more slowly than controls, and wild-type MAFB-overexpressing tumors grew more quickly than tumors overexpressing MAFB mutated at lysine 32. These data suggest that SUMOylated MAFB promotes CRC tumorigenesis through cell cycle regulation. MAFB and its SUMOylation process may serve as novel therapeutic targets for CRC treatment. Impact Journals LLC 2016-11-05 /pmc/articles/PMC5347783/ /pubmed/27829226 http://dx.doi.org/10.18632/oncotarget.13129 Text en Copyright: © 2016 Yang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Yang, Lin-Sen
Zhang, Xiao-Jian
Xie, Yin-Yin
Sun, Xiao-Jian
Zhao, Ren
Huang, Qiu-Hua
SUMOylated MAFB promotes colorectal cancer tumorigenesis
title SUMOylated MAFB promotes colorectal cancer tumorigenesis
title_full SUMOylated MAFB promotes colorectal cancer tumorigenesis
title_fullStr SUMOylated MAFB promotes colorectal cancer tumorigenesis
title_full_unstemmed SUMOylated MAFB promotes colorectal cancer tumorigenesis
title_short SUMOylated MAFB promotes colorectal cancer tumorigenesis
title_sort sumoylated mafb promotes colorectal cancer tumorigenesis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347783/
https://www.ncbi.nlm.nih.gov/pubmed/27829226
http://dx.doi.org/10.18632/oncotarget.13129
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