Breast cancer (BC) is a common reason of cancer-associated death in female. To develop novel strategy of therapeutics, it is crucial to comprehensively understand the receptor status of BC cells on the surface and inner, because chemical messengers can bind the receptors and promote tumorigenesis. Compared with normal and benign samples, BC cell lines and malignant biopsies showed higher expression of neurokinin-1 receptor (NK1). In current work, we examined the role and mechanism of NK1 receptor signaling in BC cell migration. Human hemokinin-1 (hHK-1) was the peripheral agonist of NK1 receptor. Our results showed that by activating NK1 receptor, hHK-1 promoted the migration of BC cells. Gelatin zymography and WB experiment showed that hHK-1 enhanced the levels of MMP-2 and MMP-14; inhibition of these two MMPs blocked hHK-1-induced cell migration. We further explored the underlying mechanism. hHK-1 incuced the phosphorylation of ERK1/2, JNK and Akt through PKC or PKA pathway. The phosphorylation of these kinases further regulated the activation of transcriptional factor AP-1 and NF-κB. Inhibition of AP-1 and NF-κB reduced the up-regulation of MMP-2 and MMP-14 by hHK-1. Taken together, we showed NK1 receptor was an important regulator of human BC cell migration and a potential target for BC treatment.

中文翻译：

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Neurokinin-1受体通过增加MMP-2和MMP-14的表达来介导乳腺癌细胞迁移。

乳腺癌（BC）是女性癌症相关死亡的常见原因。要开发新的治疗方法，全面了解表面和内部BC细胞的受体状态至关重要，因为化学信使可以结合受体并促进肿瘤发生。与正常和良性样品相比，BC细胞系和恶性活组织检查显示神经激肽-1受体（NK1）的表达更高。在当前的工作中，我们检查了NK1受体信号传导在BC细胞迁移中的作用和机制。人血激酶-1（hHK-1）是NK1受体的外周激动剂。我们的结果表明，通过激活NK1受体，hHK-1促进了BC细胞的迁移。明胶酶谱和WB实验表明，hHK-1能提高MMP-2和MMP-14的水平。这两个MMP的抑制作用阻止了hHK-1诱导的细胞迁移。我们进一步探讨了潜在的机制。hHK-1通过PKC或PKA途径促进ERK1 / 2，JNK和Akt的磷酸化。这些激酶的磷酸化进一步调节了转录因子AP-1和NF-κB的活化。抑制AP-1和NF-κB降低了hHK-1对MMP-2和MMP-14的上调。综上所述，我们显示NK1受体是人类BC细胞迁移的重要调节剂，并且是BC治疗的潜在靶标。