Wnt inhibitory factor-1 gene transfer inhibits melanoma cell growth

Yu Ching Lin, Liang You, Zhidong Xu, Biao He, Cheng Ta Yang, Jan Kan Chen, Iwao Mikami, Geneviève Clément, Yihui Shi, Kristopher Kuchenbecker, Junichi Okamoto, Mohammed Kashani-Sabet, David M. Jablons*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

50 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)379-386
Number of pages8
JournalHuman Gene Therapy
Volume18
Issue number4
DOIs
StatePublished - 04 2007

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