The Wnt/β-catenin pathway regulates key cellular processes such as differentiation, proliferation, apoptosis; and its activation promotes development of several cancer types. Expression of CD43 (leukosialin), the predominant leukocyte transmembrane sialoglycoprotein, has been detected
in many tumors of non-hematopoietic origin. CD43 participates in cell adhesion and regulates intracellular signal transduction pathways involved in cell proliferation and survival. The cytoplasmic domain of CD43 has been reported to translocate to the nucleus, interact with β-catenin
and affect its target gene expression, but the impact of this action on cell fate is still unknown. We demonstrate, here, by colony formation assay and siRNA-mediated gene silencing that CD43 and β-catenin co-operate in promoting cell growth. Moreover, in cells with down-regulated β-catenin
expression the activation of p53 in response to CD43 overexpression is significantly impaired. In addition, the presence of both CD43 and β-catenin is required for the TCF/LEF-mediated transcription. Presumably, the fulllength CD43 participates in this transcriptional regulation. We show
that the mature CD43 localizes to the nucleus, where it binds chromatin, co-localizes and co-immunoprecipitates with β-catenin, and enhances the reporter gene expression regulated by β-catenin. These observations provide clear evidence linking CD43 to the Wnt/APC/β-catenin signaling
pathway and supporting our hypothesis according to which CD43 plays a role in tumor development.
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Document Type: Research Article
Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia
Institute of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, 12618 Tallinn, Estonia
Publication date: January 1, 2012
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The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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