P-REX1 amplification promotes progression of cutaneous melanoma via the PAK1/P38/MMP-2 pathway.
作者： Jinhua Wang , Hajime Hirose , Guanhua Du , Kelly Chong , Eiji Kiyohara
DOI: 10.1016/J.CANLET.2017.08.001
关键词: Survivin 、 Cyclin D1 、 Cell growth 、 Cell cycle 、 Cancer research 、 RAC1 、 Molecular biology 、 Cutaneous melanoma 、 Melanoma 、 Biology 、 Tumor progression
摘要: P-REX1 (PIP3-dependent Rac exchange factor-1) is a guanine nucleotide factor that activates by catalyzing of GDP for GTP bound to Rac. Aberrant up-regulation expression has role in metastasis however, copy number (CN) and function cutaneous melanoma are unclear. To explore the melanoma, SNP 6.0 Exon 1.0 ST microarrays were assessed. There was higher CN (2.82-fold change) cells than melanocytes, significantly correlated with CN. When knocked down shRNA, proliferation, colony formation, 3D matrigel growth, migration/invasiveness inhibited. Loss inhibited cell proliferation inhibiting cyclin D1, blocking cycle, increased apoptosis reducing protein survivin. Knockdown disrupting P-REX1/RAC1/PAK1/p38/MMP-2 pathway. Assessment patient tumors disease outcome demonstrated lower distant metastasis-free survival among AJCC stage I/II/III patients high compared low expression. These results suggest plays an important tumor progression potential theranostic target.
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