Exosomal DEK removes chemoradiotherapy resistance by triggering quiescence exit of breast cancer stem cells
Exosomal DEK removes chemoradiotherapy resistance by triggering quiescence exit of breast cancer stem cells
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外泌体 DEK 通过触发乳腺癌干细胞的静止退出来消除放化疗耐药性
DOI：
10.1038/s41388-022-02278-x
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发表时间：
2022-03
期刊：
影响因子：
8
通讯作者：
Yang Wei-Jun
中科院分区：
文献类型：
--
作者：
Yang Yao-Shun;Jia Xi-Zheng;Lu Qian-Yun;Cai Sun-Li;Huang Xue-Ting;Yang Shu-Hua;Wood Chris;Wang Yue-Hong;Zhou Jiao-Jiao;Chen Yi-Ding;Yang Jin-Shu;Yang Wei-Jun
Tumor therapeutics often target the primary tumor bulk but fail to eradicate therapy-resistant cancer stem cells (CSCs) in quiescent state. These can then become activated to initiate recurrence and/or metastasis beyond therapy. Here, we identified and isolated chemoradiotherapy-resistant CSCs in quiescent state with high capacity of tumor-initiation and tumorsphere formation from three types of breast tumors in mice. Experiments of knockdown and rescue revealed DEK, a nuclear protein, as essential for CSC activation. Exogenous DEK was then used to trigger quiescence exit of CSCs. ChIP-seq and ATAC-seq showed that DEK directly binds to chromatin, facilitating its genome-wide accessibility. The resulting epigenetic events upregulate the expression of cellular activation-related genes including MYC targets, whereas cellular quiescence-related genes including the p53 signaling pathway are silenced. However, twinned with DEK-induced activation, formerly resistant CSCs were then destroyed by chemotherapy in vitro. In mice, traditional chemoradiotherapy concurrent with the injection of DEK-containing exosomes resulted in eradication of primary tumors together with formerly resistant CSCs without recurrence or metastasis. Our findings advance knowledge of the mechanism of quiescent CSC activation and may provide novel clinical opportunities for removal of quiescence-linked therapy resistance.
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DOI：
--
发表时间：
2013
期刊：
--
影响因子：
--
作者：
S. Boichuk;Joshua A. Parry;Kathleen R. Makielski;Larisa Litovchick;Julianne L. Baron;James P. Zewe;A. Wozniak;Keith R. Mehalek;N. Korzeniewski;D. Seneviratne;M. Debiec-Rychter;J. Decaprio;A. Duensing
通讯作者：
S. Boichuk;Joshua A. Parry;Kathleen R. Makielski;Larisa Litovchick;Julianne L. Baron;James P. Zewe;A. Wozniak;Keith R. Mehalek;N. Korzeniewski;D. Seneviratne;M. Debiec-Rychter;J. Decaprio;A. Duensing
影响因子：
14.9
作者：
Kavanaugh GM;Wise-Draper TM;Morreale RJ;Morrison MA;Gole B;Schwemberger S;Tichy ED;Lu L;Babcock GF;Wells JM;Drissi R;Bissler JJ;Stambrook PJ;Andreassen PR;Wiesmüller L;Wells SI
通讯作者：
Wells SI
影响因子：
3.4
作者：
Huochun Yi;Yali Liu;Pan You;Jin-Shui Pan;Jiangfan Zhou;Zhengguo Liu;Zhong-Ying Zhang
通讯作者：
Huochun Yi;Yali Liu;Pan You;Jin-Shui Pan;Jiangfan Zhou;Zhengguo Liu;Zhong-Ying Zhang
DEK 蛋白过表达预示胰腺导管腺癌预后不良
影响因子：
4.2
作者：
Sun, Jie;Bi, Fangfang;Lin, Zhenhua
通讯作者：
Lin, Zhenhua
影响因子：
64.5
作者：
Gao H;Chakraborty G;Lee-Lim AP;Mo Q;Decker M;Vonica A;Shen R;Brogi E;Brivanlou AH;Giancotti FG
通讯作者：
Giancotti FG