NAT1 promotes osteolytic metastasis in luminal breast cancer by regulating the bone metastatic niche via NF-kappa B/IL-1B signaling pathway
NAT1 promotes osteolytic metastasis in luminal breast cancer by regulating the bone metastatic niche via NF-kappa B/IL-1B signaling pathway
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NAT1通过NF-κB/IL-1B信号通路调节骨转移微环境促进管腔乳腺癌溶骨性转移
DOI：
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发表时间：
2020
影响因子：
5.3
通讯作者：
Jianru Xiao
中科院分区：
文献类型：
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作者：
Chenglong Zhao;Xiaopan Cai;Yao Wang;Dongsheng Wang;Ting Wang;Haiyi Gong;Haitao Sun;Qi Jia;Wang Zhou;Zhipeng Wu;Zhenxi Li;Jianru Xiao
乳腺癌是一种分子异质性疾病，可以细分为不同的亚型。与其他亚型相比，管腔型乳腺癌（LBC）被认为更容易发生骨转移。然而，内在机制仍然难以捉摸。生物信息学分析表明，N-乙酰基转移酶1（NAT 1）在LBC中特异性表达，并与骨转移密切相关。此外，NAT 1还能促进LBC细胞的迁移和克隆形成，诱导破骨细胞分化，提高成骨细胞的Rankl/Opg比值。我们的体内实验表明，NAT 1促进LBC骨转移和骨破坏，这可以被NAT 1抑制剂逆转。细胞因子芯片结果显示，NAT 1可显著激活NF-κB信号通路，上调IL-1 B的表达，并在此过程中发挥下游作用。以上结果表明，NAT 1在LBC中表达上调，并通过NAT 1/NF-κB/IL-1 B轴促进骨转移灶的形成和溶骨性骨转移。这一发现可能为了解LBC骨转移的机制提供了新的途径，并为其治疗提供了新的治疗和诊断靶点。
Breast cancer is a molecularly heterogeneous disease that can be subdivided into different subtypes..Compared with the other subtypes, luminal breast cancer (LBC) is considered more susceptible to bone metastasis. However, the intrinsic mechanisms remain elusive. Bioinformatics analysis of the preset study showed that.N-acetyltransferase 1 (NAT1) was specifically expressed in LBC and closely correlated with bone metastasis. In addition, NAT1 could promote LBC cell migration and clonal formation, induce osteoclast differentiation and raise the.Rankl/Opg ratio in osteoblasts. Our in vivo experiment demonstrated that NAT1 promoted LBC bone metastasis and.bone destruction, which could be reversed by NAT1 inhibitor treatment. The result of cytokine array showed that.NAT1 could significantly over activate the NF-κB signaling pathway and up-regulate the expression of IL-1B, which.further worked as downstream factors in these processes. All these results demonstrated NAT1 was up-regulated in.LBC and promoted the formation of bone metastatic niche and osteolytic bone metastasis through the NAT1/NF-κB/.IL-1B axis. This finding may provide a new pathway to help understand the mechanisms of LBC bone metastasis and.suggest a novel therapeutic and diagnostic target for its treatment.