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

doi:10.1016/s1476-5586(04)80048-4

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

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

222 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 language	English (US)
Pages (from-to)	7-14
Number of pages	8
Journal	Neoplasia
Volume	6
Issue number	1
DOIs	https://doi.org/10.1016/s1476-5586(04)80048-4
State	Published - 2004

Keywords

Apoptosis
Cancer
Human
Monoclonal antibody
Wnt-1

ASJC Scopus subject areas

Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/s1476-5586(04)80048-4

Cite this

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title = "A Monoclonal Antibody against Wnt-1 Induces Apoptosis in Human Cancer Cells",

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.",

keywords = "Apoptosis, Cancer, Human, Monoclonal antibody, Wnt-1",

author = "Biao He and Liang You and Kazutsugu Uematsu and Zhidong Xu and Lee, {Amie Y.} and Maria Matsangou and Frank McCormick and Jablons, {David M.}",

note = "Funding Information: Abbreviations: APC, adenomatous polyposis coli; Dvl, Dishevelled; GSK, glycogen synthase kinase; NHBE, normal human bronchial epithelial; NSCLC, non small cell lung cancer; RNAi, RNA interference; SAEC, small airway epithelial cell; Wnt, Wingless type Address all correspondence to: David M. Jablons, MD, Department of Surgery, Cancer Center, 1600 Divisadero Street, C322C, Box 1674, San Francisco, CA 94115, USA. E-mail: jablonsd@surgery.ucsf.edu 1This work was supported by the Larry Hall Memorial Trust and the Kazan, McClain, Edises, Abrams, Fernandez, Lyons, and Farrise Foundation. 2Current address: The Fourth Department of Internal Medicine, Nippon Medical School, Tokyo 113-8602, Japan. Received 25 July 2003; Revised 8 October 2003; Accepted 8 October 2003.",

year = "2004",

doi = "10.1016/s1476-5586(04)80048-4",

language = "English (US)",

volume = "6",

pages = "7--14",

journal = "Neoplasia",

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T1 - A Monoclonal Antibody against Wnt-1 Induces Apoptosis in Human Cancer Cells

AU - He, Biao

AU - You, Liang

AU - Uematsu, Kazutsugu

AU - Xu, Zhidong

AU - Lee, Amie Y.

AU - Matsangou, Maria

AU - McCormick, Frank

AU - Jablons, David M.

N1 - Funding Information: Abbreviations: APC, adenomatous polyposis coli; Dvl, Dishevelled; GSK, glycogen synthase kinase; NHBE, normal human bronchial epithelial; NSCLC, non small cell lung cancer; RNAi, RNA interference; SAEC, small airway epithelial cell; Wnt, Wingless type Address all correspondence to: David M. Jablons, MD, Department of Surgery, Cancer Center, 1600 Divisadero Street, C322C, Box 1674, San Francisco, CA 94115, USA. E-mail: jablonsd@surgery.ucsf.edu 1This work was supported by the Larry Hall Memorial Trust and the Kazan, McClain, Edises, Abrams, Fernandez, Lyons, and Farrise Foundation. 2Current address: The Fourth Department of Internal Medicine, Nippon Medical School, Tokyo 113-8602, Japan. Received 25 July 2003; Revised 8 October 2003; Accepted 8 October 2003.

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Cancer

KW - Human

KW - Monoclonal antibody

KW - Wnt-1

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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