SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein

The histone H3K9 methyltransferase SETDB2 is involved in cell cycle dysregulation in acute leukemia and has oncogenic roles in gastric cancer. In our study, we found that SETDB2 plays essential roles in breast cancer stem cell maintenance. Depleted SETDB2 significantly decreased the breast cancer st...

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Autores principales: Ying, Liu, Fei, Xie, Jialun, Li, Jianpeng, Xiao, Jie, Wang, Zhaolin, Mei, Hongjia, Fan, Huan, Fang, Sha, Li, Qiuju, Wu, Lin, Yuan, Cuicui, Liu, You, Peng, Weiwei, Zhao, Lulu, Wang, Jiemin, Wong, Jing, Li, Jing, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294945/
https://www.ncbi.nlm.nih.gov/pubmed/32549764
http://dx.doi.org/10.7150/ijbs.43611
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author Ying, Liu
Fei, Xie
Jialun, Li
Jianpeng, Xiao
Jie, Wang
Zhaolin, Mei
Hongjia, Fan
Huan, Fang
Sha, Li
Qiuju, Wu
Lin, Yuan
Cuicui, Liu
You, Peng
Weiwei, Zhao
Lulu, Wang
Jiemin, Wong
Jing, Li
Jing, Feng
author_facet Ying, Liu
Fei, Xie
Jialun, Li
Jianpeng, Xiao
Jie, Wang
Zhaolin, Mei
Hongjia, Fan
Huan, Fang
Sha, Li
Qiuju, Wu
Lin, Yuan
Cuicui, Liu
You, Peng
Weiwei, Zhao
Lulu, Wang
Jiemin, Wong
Jing, Li
Jing, Feng
author_sort Ying, Liu
collection PubMed
description The histone H3K9 methyltransferase SETDB2 is involved in cell cycle dysregulation in acute leukemia and has oncogenic roles in gastric cancer. In our study, we found that SETDB2 plays essential roles in breast cancer stem cell maintenance. Depleted SETDB2 significantly decreased the breast cancer stem cell population and mammosphere formation in vitro and also inhibited breast tumor initiation and growth in vivo. Restoring SETDB2 expression rescued the defect in breast cancer stem cell maintenance. A mechanistic analysis showed that SETDB2 upregulated the transcription of the ΔNp63α downstream Hedgehog pathway gene. SETDB2 also interacted with and methylated ΔNp63α, and stabilized ΔNp63α protein. Restoring ΔNp63α expression rescued the breast cancer stem cell maintenance defect which mediated by SETDB2 knockdown. In conclusion, our study reveals a novel function of SETDB2 in cancer stem cell maintenance in breast cancer.
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spelling pubmed-72949452020-06-16 SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein Ying, Liu Fei, Xie Jialun, Li Jianpeng, Xiao Jie, Wang Zhaolin, Mei Hongjia, Fan Huan, Fang Sha, Li Qiuju, Wu Lin, Yuan Cuicui, Liu You, Peng Weiwei, Zhao Lulu, Wang Jiemin, Wong Jing, Li Jing, Feng Int J Biol Sci Research Paper The histone H3K9 methyltransferase SETDB2 is involved in cell cycle dysregulation in acute leukemia and has oncogenic roles in gastric cancer. In our study, we found that SETDB2 plays essential roles in breast cancer stem cell maintenance. Depleted SETDB2 significantly decreased the breast cancer stem cell population and mammosphere formation in vitro and also inhibited breast tumor initiation and growth in vivo. Restoring SETDB2 expression rescued the defect in breast cancer stem cell maintenance. A mechanistic analysis showed that SETDB2 upregulated the transcription of the ΔNp63α downstream Hedgehog pathway gene. SETDB2 also interacted with and methylated ΔNp63α, and stabilized ΔNp63α protein. Restoring ΔNp63α expression rescued the breast cancer stem cell maintenance defect which mediated by SETDB2 knockdown. In conclusion, our study reveals a novel function of SETDB2 in cancer stem cell maintenance in breast cancer. Ivyspring International Publisher 2020-05-18 /pmc/articles/PMC7294945/ /pubmed/32549764 http://dx.doi.org/10.7150/ijbs.43611 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Ying, Liu
Fei, Xie
Jialun, Li
Jianpeng, Xiao
Jie, Wang
Zhaolin, Mei
Hongjia, Fan
Huan, Fang
Sha, Li
Qiuju, Wu
Lin, Yuan
Cuicui, Liu
You, Peng
Weiwei, Zhao
Lulu, Wang
Jiemin, Wong
Jing, Li
Jing, Feng
SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein
title SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein
title_full SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein
title_fullStr SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein
title_full_unstemmed SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein
title_short SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein
title_sort setdb2 promoted breast cancer stem cell maintenance by interaction with and stabilization of δnp63α protein
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294945/
https://www.ncbi.nlm.nih.gov/pubmed/32549764
http://dx.doi.org/10.7150/ijbs.43611
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