Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 312K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chen, S. Articles by Wang, C.-Y. Search for Related Content PubMed PubMed Citation Articles by Chen, S. Articles by Wang, C.-Y. Related Collections Related Article Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/2001//87 $5.00
The Journal of Cell Biology, Volume 152, Number 1, , 2001 87-96

WNT-1 Signaling Inhibits Apoptosis by Activating β-Catenin/T Cell Factor–Mediated Transcription

^a Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences,
^b Program in Cellular and Molecular Biology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109
^c Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27519
^d Department of Biochemistry and Medicine, Charlottesville, Virginia 22908-0733
^e Department of Pathology and Obstetrics and Gynecology, College of Physician and Surgeons, Columbia University, New York, New York 10032
Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences, Room 5223, Box 1078, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078.(734)-764-2425(734) 615-4386

cunywang{at}umich.edu

Wnt signaling plays a critical role in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of Wnt signaling, little is known regarding Wnt signaling modification of the cell death machinery. Given that numerous oncogenes transform cells by providing cell survival function, we hypothesized that Wnt signaling may inhibit apoptosis. Here, we report that cells expressing Wnt-1 were resistant to cancer therapy–mediated apoptosis. Wnt-1 signaling inhibited the cytochrome c release and the subsequent caspase-9 activation induced by chemotherapeutic drugs, including both vincristine and vinblastine. Furthermore, we found that Wnt-1–mediated cell survival was dependent on the activation of β-catenin/T cell factor (Tcf) transcription. Inhibition of β-catenin/Tcf transcription by expression of the dominant-negative mutant of Tcf-4 blocked Wnt-1–mediated cell survival and rendered cells sensitive to apoptotic stimuli. These results provide the first demonstration that Wnt-1 inhibits cancer therapy–mediated apoptosis and suggests that Wnt-1 may exhibit its oncogenic potential through a mechanism of anti-apoptosis.

Key Words: β-catenin • apoptosis • Wnt signaling • Tcf transcription • cytochrome c

© 2001 The Rockefeller University Press

Abbreviations used in this paper: Apaf-1, apoptotic protease–activating factor-1; APC, adenomatous polyposis coli; β-gal, β-galactosidase; DN, dominant-negative mutant; EGFP, enhanced green fluorescent protein; GFP, green fluorescent protein; GSK-3β, glycogen synthase kinase-3β; IAP, inhibitors of apoptosis; IB, inhibitor of B; IKK, IB kinase; JNK, c-Jun NH₂-terminal kinase; Lef, lymphocyte enhancer factor; NF-B, nuclear factor kappa B; PI, propidium iodide; PI3K, phosphatidyinositol-3 kinase; PS, phosphatidylserine; Tcf, T cell factor; TNF, tumor necrosis factor; VCR, vincristine; VBL, vinblastine.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents