title: Neurokinin-1 receptor mediated breast cancer cell migration by increased expression of MMP-2 and MMP-14.
abstract: 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.
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China.
authors: Jingyi
authors: J
authors: Li
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China.
authors: Qian
authors: Q
authors: Zeng
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China.
authors: Yixin
authors: Y
authors: Zhang
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China.
authors: Xiaofang
authors: X
authors: Li
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China.
authors: Hui
authors: H
authors: Hu
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China.
authors: Xiaokang
authors: X
authors: Miao
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China.
authors: Wenle
authors: W
authors: Yang
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China.
authors: Wei
authors: W
authors: Zhang
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China.
authors: Xiaoyun
authors: X
authors: Song
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China. Electronic address: muly@lzu.edu.cn.
authors: Lingyun
authors: L
authors: Mou
authors: Institute of Biochemistry and Molecular Biology, School of Life Sciences and Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China. Electronic address: wangrui@lzu.edu.cn.
authors: Rui
authors: R
authors: Wang
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D015320:Tachykinins / Q000378:metabolism
chemical_list: D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C507968:hemokinin-1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: Breast cancer; Cell migration; Hemokinin-1; Matrix metalloproteinases; Neurokinin-1 receptor