Wnt inhibitory factor-1 gene transfer inhibits melanoma cell growth.
Silencing of Wnt antagonists with aberrant activation of Wnt signaling is a common phenomenon in various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. In this study, we tried to illuminate the impact of WIF-1 gene expression in melanoma with WIF-1 silencing by in vitro and in vivo studies. We restored the expression of WIF-1 by nonviral gene transfer with a pcDNA3.1 vector. We demonstrated inhibition of melanoma cell growth after WIF-1 restoration in colony formation and proliferation assays in vitro. In addition, the inhibitory effect was related to downregulation of Wnt signaling, which was demonstrated at both the transcriptional and translational levels. Furthermore, by using a xenograft mouse model, we confirmed the effect of WIF-1 expression in suppressing tumor growth by inhibition of Wnt signaling in vivo. Our results suggest the potential for further application of WIF-1 gene therapy in melanoma with WIF-1 silencing.
Lin
Yu-Ching
YC
Thoracic Oncology Laboratory, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, USA.
You
Liang
L
Xu
Zhidong
Z
He
Biao
B
Yang
Cheng-Ta
CT
Chen
Jan-Kan
JK
Mikami
Iwao
I
Clément
Geneviève
G
Shi
Yihui
Y
Kuchenbecker
Kristopher
K
Okamoto
Junichi
J
Kashani-Sabet
Mohammed
M
Jablons
David M
DM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D019175:DNA Methylation; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D048868:Adaptor Proteins, Signal Transducing; D012097:Repressor Proteins; C485569:WIF1 protein, human