title: Human hemokinin-1 promotes migration of melanoma cells and increases MMP-2 and MT1-MMP expression by activating tumor cell NK1 receptors.
abstract: Receptors and their regulatory peptides are aberrantly expressed in tumors, suggesting a potential tumor therapy target. Human hemokinin-1 (hHK-1) is a tachykinin peptide ligand of the neurokinin-1 (NK1) receptor which is overexpressed in melanoma and other tumor tissues. Here, we investigated the role of hHK-1 and the NK1 receptor in melanoma cell migration. NK1 receptor expression was associated with melanoma metastatic potential. Treatment with hHK-1 significantly enhanced A375 and B16F10 melanoma cell migration and an NK1 receptor antagonist L732138 blocked this effect. MMP-2 and MT1-MMP expression were up-regulated in hHK-1-treated melanoma cells and cell signaling data suggested that hHK-1 induced phosphorylation of ERK1/2, JNK and p38 by way of PKC or PKA. Kinase activation led to increased MMP-2 and MT1-MMP expression and melanoma cell migration induced by hHK-1. Thus, hHK-1 and the NK1 receptor are critical to melanoma cell migration and each may be a promising chemotherapeutic target.
authors.affiliation: 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.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.forename: Xiaofang
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.forename: Jingyi
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.forename: Hui
authors.initials: H
authors.lastname: Hu
authors.affiliation: 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.forename: Xiaokang
authors.initials: X
authors.lastname: Miao
authors.affiliation: 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.forename: Xiaoyun
authors.initials: X
authors.lastname: Song
authors.affiliation: 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.forename: Wenle
authors.initials: W
authors.lastname: Yang
authors.affiliation: 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.forename: Qian
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: 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.forename: Lingyun
authors.initials: L
authors.lastname: Mou
authors.affiliation: 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.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008024:Ligands; D053511:Matrix Metalloproteinase 14 / Q000235:genetics*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D064729:Neurokinin-1 Receptor Antagonists / Q000008:administration & dosage; D010766:Phosphorylation; D018040:Receptors, Neurokinin-1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015320:Tachykinins / Q000235:genetics* / Q000378:metabolism
chemical_list: D008024:Ligands; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C507968:hemokinin-1; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: Cell migration; Hemokinin-1; Matrix metalloproteinases; Melanoma; Neurokinin-1 receptor