SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of Δnp63α protein

Liu Ying; Xie Fei; Li Jialun; Xiao Jianpeng; Wang Jie; Mei Zhaolin; Fan Hongjia; Fang Huan; Li Sha; Wu Qiuju; Yuan Lin; Liu Cuicui; Peng You; Zhao Weiwei; Wang Lulu; Wong Jiemin; Li Jing; Feng Jing

doi:10.7150/ijbs.43611

SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of Δnp63α protein

Liu Ying
, Xie Fei
, Li Jialun
, Xiao Jianpeng
, Wang Jie
, Mei Zhaolin
, Fan Hongjia
, Fang Huan
, Li Sha
, Wu Qiuju
, Yuan Lin
, Liu Cuicui
, Peng You
, Zhao Weiwei
, Wang Lulu
, Wong Jiemin
, Li Jing^*
, Feng Jing^*

^*此作品的通讯作者

生命科学学院

Anhui University of Science and Technology
Hubei University of Medicine
Shanghai University of Medicine and Health Sciences
East China Normal University
Southern Medical University
Southern Medical University Affiliated Fengxian Hospital
Shanghai Jiao Tong University

科研成果: 期刊稿件 › 文章 › 同行评审

15 引用（Scopus）

摘要

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.

源语言	英语
页（从-至）	2180-2191
页数	12
期刊	International Journal of Biological Sciences
卷	16
期	12
DOI	https://doi.org/10.7150/ijbs.43611
出版状态	已出版 - 2020

联合国可持续发展目标

此成果有助于实现下列可持续发展目标：

可持续发展目标 3 良好健康与福祉

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10.7150/ijbs.43611

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引用此

Ying, L., Fei, X., Jialun, L., Jianpeng, X., Jie, W., Zhaolin, M., Hongjia, F., Huan, F., Sha, L., Qiuju, W., Lin, Y., Cuicui, L., You, P., Weiwei, Z., Lulu, W., Jiemin, W., Jing, L., & Jing, F. (2020). SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of Δnp63α protein. International Journal of Biological Sciences, 16(12), 2180-2191. https://doi.org/10.7150/ijbs.43611

@article{fa9583e050f641ff91d3740da2ffc412,

title = "SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of Δnp63α protein",

abstract = "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.",

keywords = "Breast cancer stem cell, Hedgehog pathway, SETDB2, Stability, ΔNp63α",

author = "Liu Ying and Xie Fei and Li Jialun and Xiao Jianpeng and Wang Jie and Mei Zhaolin and Fan Hongjia and Fang Huan and Li Sha and Wu Qiuju and Yuan Lin and Liu Cuicui and Peng You and Zhao Weiwei and Wang Lulu and Wong Jiemin and Li Jing and Feng Jing",

note = "Publisher Copyright: {\textcopyright} The author(s).",

year = "2020",

doi = "10.7150/ijbs.43611",

language = "英语",

volume = "16",

pages = "2180--2191",

journal = "International Journal of Biological Sciences",

issn = "1449-2288",

publisher = "Ivyspring International Publisher",

number = "12",

}

Ying, L, Fei, X, Jialun, L, Jianpeng, X, Jie, W, Zhaolin, M, Hongjia, F, Huan, F, Sha, L, Qiuju, W, Lin, Y, Cuicui, L, You, P, Weiwei, Z, Lulu, W, Jiemin, W, Jing, L & Jing, F 2020, 'SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of Δnp63α protein', International Journal of Biological Sciences, 卷 16, 号码 12, 页码 2180-2191. https://doi.org/10.7150/ijbs.43611

TY - JOUR

T1 - SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of Δnp63α protein

AU - Ying, Liu

AU - Fei, Xie

AU - Jialun, Li

AU - Jianpeng, Xiao

AU - Jie, Wang

AU - Zhaolin, Mei

AU - Hongjia, Fan

AU - Huan, Fang

AU - Sha, Li

AU - Qiuju, Wu

AU - Lin, Yuan

AU - Cuicui, Liu

AU - You, Peng

AU - Weiwei, Zhao

AU - Lulu, Wang

AU - Jiemin, Wong

AU - Jing, Li

AU - Jing, Feng

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Breast cancer stem cell

KW - Hedgehog pathway

KW - SETDB2

KW - Stability

KW - ΔNp63α

UR - https://www.scopus.com/pages/publications/85086686914

U2 - 10.7150/ijbs.43611

DO - 10.7150/ijbs.43611

M3 - 文章

C2 - 32549764

AN - SCOPUS:85086686914

SN - 1449-2288

VL - 16

SP - 2180

EP - 2191

JO - International Journal of Biological Sciences

JF - International Journal of Biological Sciences

IS - 12

ER -

SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of Δnp63α protein

摘要

联合国可持续发展目标

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