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首页> 外文期刊>Oncogene >HOXB13 downregulates intracellular zinc and increases NF-|[kappa]|B signaling to promote prostate cancer metastasis
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HOXB13 downregulates intracellular zinc and increases NF-|[kappa]|B signaling to promote prostate cancer metastasis

机译：HOXB13下调细胞内锌并增加NF- |κ| B信号传导，促进前列腺癌转移

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Characteristically, prostate cancer (PCa) cells exhibit marked decrease in intracellular zinc; however, the mechanism responsible is not clearly understood. HOXB13 is involved in PCa progression and is overexpressed in castration-resistant PCa. DNA microarray analysis of LNCaP Pca cells showed that ZnT zinc output transporters were strikingly upregulated among androgen-independent HOXB13 target genes. Furthermore, exogenous HOXB13 caused intracellular zinc concentrations to fall in PCa cells, stimulated NF-κB-mediated signaling by reducing inhibitor of NF-κB alpha (IκBα) and enhanced the nuclear translocation of RelA/p65. Human prostate tumors also exhibited strong inverse correlation between the protein expressions of HOXB13 and IκBα. Consequently, HOXB13 stimulated PCa cell invasion, and this was inhibited by the suppression of ZnT4. In addition, studies in a PC3 orthotopic mouse model of PCa metastasis showed that HOXB13 is a strong metastatic stimulator. Taken together, these results show that HOXB13 promotes PCa invasion and metastasis by decreasing intracellular zinc levels, thus stimulating NF-κB signals, and suggest that HOXB13 acts as a modulator of intracellular zinc levels that promotes the malignant characteristics of PCa.
机译：特征在于，前列腺癌（PCa）细胞的细胞内锌含量显着下降。但是，责任机制尚不清楚。 HOXB13参与PCa的进程，在去势抵抗性PCa中过表达。 LNCaP Pca细胞的DNA芯片分析表明，锌依赖性锌输出转运蛋白在雄激素非依赖性HOXB13靶基因中显着上调。此外，外源性HOXB13导致PCa细胞中的细胞内锌浓度下降，通过减少NF-κBα（IκBα）抑制剂刺激了NF-κB介导的信号传导，并增强了RelA / p65的核易位。人前列腺肿瘤还表现出HOXB13和IκBα的蛋白质表达之间的强负相关。因此，HOXB13刺激PCa细胞侵袭，并且被ZnT4抑制所抑制。此外，对PC3转移的PC3原位小鼠模型的研究表明，HOXB13是一种强大的转移刺激剂。综上所述，这些结果表明HOXB13通过降低细胞内锌水平从而促进NF-κB信号来促进PCa侵袭和转移，并表明HOXB13充当细胞内锌水平的调节剂，其促进了PCa的恶性特征。

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