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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Bibliographic Details
Published in:International journal of biological sciences 2020-01, Vol.16 (12), p.2180-2191
Main Authors: 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
Format: Article
Language:English
Subjects:
Antibodies
Breast cancer
Cell cycle
Cell growth
Flags
Gastric cancer
Glycerol
Histone methyltransferase
Leukemia
Maintenance
Medical research
Metastasis
Methyltransferase
Plasmids
Proteins
Reagents
Research Paper
Roles
Stem cells
Transcription
Tumorigenesis
Tumors
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Summary: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 and also inhibited breast tumor initiation and growth . 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.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.43611