NKX2-8/PTHrP Axis-Mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer.
NKX2-8/PTHrP Axis-Mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer.
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DOI：
10.3389/fonc.2022.907000
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发表时间：
2022
影响因子：
4.7
通讯作者：
Li, Jun
中科院分区：
文献类型：
--
作者：
Abudourousuli, Ainiwaerjiang;Chen, Suwen;Hu, Yameng;Qian, Wanying;Liao, Xinyi;Xu, Yingru;Song, Libing;Zhang, Shuxia;Li, Jun
Bone metastasis is one of the most common distant metastasis of breast cancer, which could cause serious skeletal disease and increased cancer-related death. Therefore, identification of novel target(s) to develop therapeutics would improve patient outcomes. The role of NKX2-8 in modulation of bone remodeling was determined using osteoclastogenesis and micro-CT assays. The expression of NKX2-8 was examined via immunohistochemistry analysis in 344 breast cancer tissues. The mechanism underlying NKX2-8-mediated PTHrP downregulation was investigated using biotinylated deactivated Cas9 capture analysis, chromatin immunoprecipitation, co-immunoprecipitation assays. A bone-metastatic mouse model was used to examine the effect of NKX2-8 dysregulation on breast cancer bone metastasis and the impact of three PTHrP inhibitor on prevention of breast cancer bone metastasis. The downregulated expression of NKX2-8 was significantly correlated with breast cancer bone metastasis. In vivo bone-metastatic mouse model indicated that silencing NKX2-8 promoted, but overexpressing NKX2-8 inhibited, breast cancer osteolytic bone metastasis and osteoclastogenesis. Mechanistically, NKX2-8 directly interacted with HDAC1 on the PTHrP promoter, which resulted in a reduction of histone H3K27 acetylation, consequently transcriptionally downregulated PTHrP expression in breast cancer cells. Furthermore, targeting PTHrP effectively inhibited NKX2-8-downregulation-mediated breast cancer bone metastasis. Taken together, our results uncover a novel mechanism underlying NKX2-8 downregulation-mediated breast cancer bone metastasis and represent that the targeting PTHrP might be a tailored treatment for NKX2-8 silencing-induced breast cancer bone metastasis.
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影响因子：
11.2
作者：
Nakajima K;Kho DH;Yanagawa T;Harazono Y;Hogan V;Chen W;Ali-Fehmi R;Mehra R;Raz A
通讯作者：
Raz A
通过生物素化 dCas9 原位捕获染色质相互作用
影响因子：
64.5
作者：
Liu X;Zhang Y;Chen Y;Li M;Zhou F;Li K;Cao H;Ni M;Liu Y;Gu Z;Dickerson KE;Xie S;Hon GC;Xuan Z;Zhang MQ;Shao Z;Xu J
通讯作者：
Xu J
影响因子：
27.4
作者：
Jones, DH;Kong, YY;Penninger, JM
通讯作者：
Penninger, JM
影响因子：
2.9
作者：
Cetin K;Christiansen CF;Sværke C;Jacobsen JB;Sørensen HT
通讯作者：
Sørensen HT
影响因子：
8
作者：
Hagihara, A;Miyamoto, K;Ushijima, T
通讯作者：
Ushijima, T