KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer

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	KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer
	Yu, B; Luo, F; Sun, BW; Liu, WX; Shi, QQ; Cheng, SY; Chen, CS; Chen, GQ; Li, YX; Feng, HZ
	2021
发表期刊	ADVANCED SCIENCE
卷号	8 期号:20
摘要	Aberrant SMAD3 activation has been implicated as a driving event in cancer metastasis, yet the underlying mechanisms are still elusive. Here, SMAD3 is identified as a nonhistone substrate of lysine acetyltransferase 6A (KAT6A). The acetylation of SMAD3 at K20 and K117 by KAT6A promotes SMAD3 association with oncogenic chromatin modifier tripartite motif-containing 24 (TRIM24) and disrupts SMAD3 interaction with tumor suppressor TRIM33. This event in turn promotes KAT6A-acetylated H3K23-mediated recruitment of TRIM24-SMAD3 complex to chromatin and thereby increases SMAD3 activation and immune response-related cytokine expression, leading to enhanced breast cancer stem-like cell stemness, myeloid-derived suppressor cell (MDSC) recruitment, and triple-negative breast cancer (TNBC) metastasis. Inhibiting KAT6A in combination with anti-PD-L1 therapy in treating TNBC xenograft-bearing animals markedly attenuates metastasis and provides a significant survival benefit. Thus, the work presents a KAT6A acetylation-dependent regulatory mechanism governing SMAD3 oncogenic function and provides insight into how targeting an epigenetic factor with immunotherapies enhances the antimetastasis efficacy.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13694
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Yu, B,Luo, F,Sun, BW,et al. KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer[J]. ADVANCED SCIENCE,2021,8(20).
APA	Yu, B.,Luo, F.,Sun, BW.,Liu, WX.,Shi, QQ.,...&Feng, HZ.(2021).KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer.ADVANCED SCIENCE,8(20).
MLA	Yu, B,et al."KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer".ADVANCED SCIENCE 8.20(2021).

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