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^*

^*Corresponding author for this work

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English
Pages (from-to)	2180-2191
Number of pages	12
Journal	International Journal of Biological Sciences
Volume	16
Issue number	12
DOIs	https://doi.org/10.7150/ijbs.43611
State	Published - 2020

Keywords

Breast cancer stem cell
Hedgehog pathway
SETDB2
Stability
ΔNp63α

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7150/ijbs.43611

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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, vol. 16, no. 12, pp. 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

Abstract

Keywords

UN SDGs

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