Ocular albinism type 1-induced melanoma cell migration is mediated through the RAS/RAF/MEK/ERK signaling pathway

被引:21
作者
Bai, Jun [1 ]
Xie, Xin [2 ,3 ]
Lei, Yun [1 ]
An, Gaili [1 ]
He, Li [1 ]
Lv, Xiaopeng [3 ]
机构
[1] Xi An Jiao Tong Univ, Dept Med Oncol, Shaanxi Prov Peoples Hosp, Affiliated Hosp 3,Sch Med, Xian 710068, Shaanxi, Peoples R China
[2] NW Univ Xian, Coll Life Sci, Minist Educ, Key Lab Resource Biol & Biotechnol Western China, Xian 710069, Shaanxi, Peoples R China
[3] Inst Integrated Med Informat, Dept Translat Med, Xian 710016, Shaanxi, Peoples R China
关键词
ocular albinism type 1; melanoma; migration; RAS/RAF/mitogen activated protein kinase kinase/extracellular signal-regulated kinase signaling pathway; PROTEIN; MUTATIONS; APOPTOSIS; TRANSPORT; SURVIVIN; RECEPTOR; GENE;
D O I
10.3892/mmr.2014.2154
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Malignant melanoma has the highest risk of mortality among all types of skin cancer due to its highly metastatic potential. The ocular albinism type 1 (OA1) protein is a pigment cell-specific glycoprotein, which shares significant structural and functional features with G protein-coupled receptors. However, the role of OA1 in melanoma has yet to be elucidated. The present study aimed to investigate whether OA1 is involved in melanoma cell migration. OA1 was found to stimulate cell migration in a dose-dependent manner in cultured human melanoma cells. Furthermore, knockdown of OA1 using small interfering RNA was observed to significantly inhibit melanoma cell migration. In addition, the mechanism underlying OA1-induced melanoma cell migration was investigated. Stimulation of the RAS/RAF/mitogen activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway using growth factors enhanced OA1 expression and melanoma cell migration, whereas inhibition of this pathway using U0126 was observed to markedly decrease OA1 expression and the number of migrated cells. These findings indicate that OA1 is involved in melanoma cell migration and that OA1-induced melanoma cell migration is mediated through the RAS/RAF/MEK/ERK signaling pathway. Therefore, OA1 may serve as a novel therapeutic target for melanoma.
引用
收藏
页码:491 / 495
页数:5
相关论文
共 25 条
[1]   Modulation of the Ras/Raf/MEK/ERK pathway by Ca2+, and calmodulin [J].
Agell, N ;
Bachs, O ;
Rocamora, N ;
Villalonga, P .
CELLULAR SIGNALLING, 2002, 14 (08) :649-654
[2]   A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma [J].
Ambrosini, G ;
Adida, C ;
Altieri, DC .
NATURE MEDICINE, 1997, 3 (08) :917-921
[3]  
Bhatia S, 2009, ONCOLOGY-NY, V23, P488
[4]   The molecular pathology of cutaneous melanoma [J].
Bogenrieder, Thomas ;
Herlyn, Meenhard .
CANCER BIOMARKERS, 2011, 9 (1-6) :267-286
[5]   Molecular targeted therapies in metastatic melanoma [J].
Chakraborty, Rima ;
Wieland, Carilyn N. ;
Comfere, Nneka I. .
PHARMACOGENOMICS & PERSONALIZED MEDICINE, 2013, 6 :49-56
[6]   Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention [J].
Chang, F ;
Steelman, LS ;
Lee, JT ;
Shelton, JG ;
Navolanic, PM ;
Blalock, WL ;
Franklin, RA ;
McCubrey, JA .
LEUKEMIA, 2003, 17 (07) :1263-1293
[7]   Raf Kinase Inhibitor RKIP Inhibits MDA-9/Syntenin-Mediated Metastasis in Melanoma [J].
Das, Swadesh K. ;
Bhutia, Sujit K. ;
Sokhi, Upneet K. ;
Azab, Belal ;
Su, Zhao-zhong ;
Boukerche, Habib ;
Anwar, Talha ;
Moen, Erika L. ;
Chatterjee, Devasis ;
Pellecchia, Maurizio ;
Sarkar, Devanand ;
Fisher, Paul B. .
CANCER RESEARCH, 2012, 72 (23) :6217-6226
[8]   Mutations of the BRAF gene in human cancer [J].
Davies, H ;
Bignell, GR ;
Cox, C ;
Stephens, P ;
Edkins, S ;
Clegg, S ;
Teague, J ;
Woffendin, H ;
Garnett, MJ ;
Bottomley, W ;
Davis, N ;
Dicks, N ;
Ewing, R ;
Floyd, Y ;
Gray, K ;
Hall, S ;
Hawes, R ;
Hughes, J ;
Kosmidou, V ;
Menzies, A ;
Mould, C ;
Parker, A ;
Stevens, C ;
Watt, S ;
Hooper, S ;
Wilson, R ;
Jayatilake, H ;
Gusterson, BA ;
Cooper, C ;
Shipley, J ;
Hargrave, D ;
Pritchard-Jones, K ;
Maitland, N ;
Chenevix-Trench, G ;
Riggins, GJ ;
Bigner, DD ;
Palmieri, G ;
Cossu, A ;
Flanagan, A ;
Nicholson, A ;
Ho, JWC ;
Leung, SY ;
Yuen, ST ;
Weber, BL ;
Siegler, HF ;
Darrow, TL ;
Paterson, H ;
Marais, R ;
Marshall, CJ ;
Wooster, R .
NATURE, 2002, 417 (6892) :949-954
[9]   Pigmentation-related genes and their implication in malignant melanoma susceptibility [J].
Fernandez, Lara P. ;
Milne, Roger L. ;
Pita, Guillermo ;
Floristan, Uxua ;
Sendagorta, Elena ;
Feito, Marta ;
Aviles, Jose A. ;
Martin-Gonzalez, Manuel ;
Lazaro, Pablo ;
Benitez, Javier ;
Ribas, Gloria .
EXPERIMENTAL DERMATOLOGY, 2009, 18 (07) :634-642
[10]   Melanoma incidence and mortality in Europe: new estimates, persistent disparities [J].
Forsea, A. M. ;
del Marmol, V. ;
de Vries, E. ;
Bailey, E. E. ;
Geller, A. C. .
BRITISH JOURNAL OF DERMATOLOGY, 2012, 167 (05) :1124-1130