A Monoclonal Antibody against Wnt-1 Induces Apoptosis in Human Cancer Cells

Biao He, Liang You, Kazutsugu Uematsu, Zhidong Xu, Amie Y. Lee, Maria Matsangou, Frank McCormick, David M. Jablons*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

205 Scopus citations

Abstract

Aberrant activation of the Wingless-type (Wnt)/β-catenin signaling pathway is associated with a variety of human cancers. Little is known regarding the role that Wnt ligands play in human carcinogenesis. To test whether a Wnt-1 signal is a survival factor in human cancer cells and thus may serve as a potential cancer therapeutic target, we investigated the effect of inhibition of Wnt-1 signaling in a variety of human cancer cell lines, including non small cell lung cancer, breast cancer, mesothelioma, and sarcoma. Both monoclonal antibody and RNA interference (RNAi) were used to inhibit Wnt-1 signaling. We found that incubation of a monoclonal anti-Wnt-1 antibody induced apoptosis and caused downstream protein changes in cancer cells overexpressing Wnt-1. In contrast, apoptosis was not detected in cells lacking or having minimal Wnt-1 expression after the antibody incubation. RNAi targeting of Wnt-1 in cancer cells overexpressing Wnt-1 demonstrated similar downstream protein changes and induction of apoptosis. The antibody also suppressed tumor growth in vivo. Our results indicate that both monoclonal anti-Wnt-1 antibody and Wnt-1 siRNA inhibit Wnt-1 signaling and can induce apoptosis in human cancer cells. These findings hold promise as a novel therapeutic strategy for cancer.

Original languageEnglish (US)
Pages (from-to)7-14
Number of pages8
JournalNeoplasia
Volume6
Issue number1
DOIs
StatePublished - 2004

Keywords

  • Apoptosis
  • Cancer
  • Human
  • Monoclonal antibody
  • Wnt-1

ASJC Scopus subject areas

  • Cancer Research

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