@article{dc998267c0934c44afe647948b9133aa,
title = "P-REX1 amplification promotes progression of cutaneous melanoma via the PAK1/P38/MMP-2 pathway",
abstract = "P-REX1 (PIP3-dependent Rac exchange factor-1) is a guanine nucleotide exchange factor that activates Rac by catalyzing exchange of GDP for GTP bound to Rac. Aberrant up-regulation of P-REX1 expression has a role in metastasis however, copy number (CN) and function of P-REX1 in cutaneous melanoma are unclear. To explore the role of P-REX1 in melanoma, SNP 6.0 and Exon 1.0 ST microarrays were assessed. There was a higher CN (2.82-fold change) of P-REX1 in melanoma cells than in melanocytes, and P-REX1 expression was significantly correlated with P-REX1 CN. When P-REX1 was knocked down in cells by P-REX1 shRNA, proliferation, colony formation, 3D matrigel growth, and migration/invasiveness were inhibited. Loss of P-REX1 inhibited cell proliferation by inhibiting cyclin D1, blocking cell cycle, and increased cell apoptosis by reducing expression of the protein survivin. Knockdown of P-REX1 expression inhibited cell migration/invasiveness by disrupting P-REX1/RAC1/PAK1/p38/MMP-2 pathway. Assessment of patient tumors and disease outcome demonstrated lower distant metastasis-free survival among AJCC stage I/II/III patients with high P-REX1 expression compared to patients with low P-REX1 expression. These results suggest P-REX1 plays an important role in tumor progression and a potential theranostic target.",
keywords = "Copy number, Melanoma, P-REX1, PAK1/p38/MMP-2",
author = "Jinhua Wang and Hajime Hirose and Guanhua Du and Kelly Chong and Eiji Kiyohara and Witz, {Isaac P.} and Hoon, {Dave S.B.}",
note = "Publisher Copyright: {\textcopyright} 2017",
year = "2017",
month = oct,
day = "28",
doi = "10.1016/j.canlet.2017.08.001",
language = "אנגלית",
volume = "407",
pages = "66--75",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
}