Neurokinin-1 receptor mediated breast cancer cell migration by increased expression of MMP-2 and MMP-14
Neurokinin-1 receptor mediated breast cancer cell migration by increased expression of MMP-2 and MMP-14
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DOI：
10.1016/j.ejcb.2016.07.005
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发表时间：
2016-10-01
影响因子：
6.6
通讯作者：
Wang, Rui
中科院分区：
文献类型：
--
作者：
Li, Jingyi;Zeng, Qian;Wang, Rui
乳腺癌（Breast cancer，BC）是女性癌症死亡的常见原因。为了开发新的治疗策略，全面了解BC细胞表面和内部的受体状态是至关重要的，因为化学信使可以结合受体并促进肿瘤的发生。与正常和良性肿瘤相比，BC细胞系和恶性肿瘤活检组织中神经激肽1受体（NK 1）的表达更高。在目前的工作中，我们研究了NK 1受体信号传导在BC细胞迁移中的作用和机制。人血激肽-1（hHK-1）是NK 1受体的外周激动剂。结果表明，hHK-1通过激活NK 1受体促进BC细胞的迁移。明胶酶谱和WB实验表明，hHK-1可增强MMP-2和MMP-14的表达，抑制这两种MMP可阻断hHK-1诱导的细胞迁移。我们进一步探索了潜在的机制。hHK-1通过PKC或PICA途径诱导ERK 1/2、JNK和Akt磷酸化。这些激酶的磷酸化进一步调节转录因子AP-1和NF-κ B B的活化。抑制AP-1和NF-κ B可降低hHK-1对MMP-2和MMP-14的上调作用。总之，我们表明NK 1受体是人BC细胞迁移的重要调节因子，也是BC治疗的潜在靶点。(C)2016年爱思唯尔有限公司。All rights reserved.
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 PICA pathway. The phosphorylation of these kinases further regulated the activation of transcriptional factor AP-1 and NF-kappa B. Inhibition of AP-1 and NF-kappa B 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. (C) 2016 Elsevier GmbH. All rights reserved.