SOSTDC1 Nuclear Translocation Facilitates BTIC Maintenance and CHD1-Mediated HR Repair to Promote Tumor Progression and Olaparib Resistance in TNBC

KIZ OpenIR > 科研部门 > 肿瘤生物学（陈策实）

	SOSTDC1 Nuclear Translocation Facilitates BTIC Maintenance and CHD1-Mediated HR Repair to Promote Tumor Progression and Olaparib Resistance in TNBC
	Deng, QD; Qiang, JK; Liu, CC; Ding, JJ; Tu, JCL; He, XY; Xia, J; Peng, XL; Li, SQ; Chen, X; Ma, W; Zhang, L; Jiang, YZ; Shao, ZM; Chen, CS; Liu, SL; Xu, JH; Zhang, LX
	2024
发表期刊	ADVANCED SCIENCE
ISSN	2198-3844
摘要	Breast tumor-initiating cells (BTICs) of triple-negative breast cancer (TNBC) tissues actively repair DNA and are resistant to treatments including chemotherapy, radiotherapy, and targeted therapy. Herein, it is found that a previously reported secreted protein, sclerostin domain containing 1 (SOSTDC1), is abundantly expressed in BTICs of TNBC cells and positively correlated with a poor patient prognosis. SOSTDC1 knockdown impairs homologous recombination (HR) repair, BTIC maintenance, and sensitized bulk cells and BTICs to Olaparib. Mechanistically, following Olaparib treatment, SOSTDC1 translocates to the nucleus in an importin-alpha dependent manner. Nuclear SOSTDC1 interacts with the N-terminus of the nucleoprotein, chromatin helicase DNA-binding factor (CHD1), to promote HR repair and BTIC maintenance. Furthermore, nuclear SOSTDC1 bound to beta-transducin repeat-containing protein (beta-TrCP) binding motifs of CHD1 is found, thereby blocking the beta-TrCP-CHD1 interaction and inhibiting beta-TrCP-mediated CHD1 ubiquitination and degradation. Collectively, these findings identify a novel nuclear SOSTDC1 pathway in regulating HR repair and BTIC maintenance, providing insight into the TNBC therapeutic strategies. In this study, SOSTDC1 is identified as a potential target mediating BTICs resistance to Olaparib. SOSTDC1 is highly expressed in TNBC tissues and especially in the BTIC population. Nuclear translocation of SOSTDC1 mediated by importin-alpha stabilizes CHD1 protein from ubiquitination, thereby promoting HR repair, BTIC maintenance, and Olaparib resistance in TNBC. image
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/152453/14229
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Deng, QD,Qiang, JK,Liu, CC,et al. SOSTDC1 Nuclear Translocation Facilitates BTIC Maintenance and CHD1-Mediated HR Repair to Promote Tumor Progression and Olaparib Resistance in TNBC[J]. ADVANCED SCIENCE,2024.
APA	Deng, QD.,Qiang, JK.,Liu, CC.,Ding, JJ.,Tu, JCL.,...&Zhang, LX.(2024).SOSTDC1 Nuclear Translocation Facilitates BTIC Maintenance and CHD1-Mediated HR Repair to Promote Tumor Progression and Olaparib Resistance in TNBC.ADVANCED SCIENCE.
MLA	Deng, QD,et al."SOSTDC1 Nuclear Translocation Facilitates BTIC Maintenance and CHD1-Mediated HR Repair to Promote Tumor Progression and Olaparib Resistance in TNBC".ADVANCED SCIENCE (2024).

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