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Novel roles of Hakai in cell proliferation and oncogenesis

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Item Type:Article
Title:Novel roles of Hakai in cell proliferation and oncogenesis
Creators Name:Figueroa, A., Kotani, H., Toda, Y., Mazan-Mamczarz, K., Mueller, E.C., Otto, A., Disch, L., Norman, M., Ramdasi, R., Keshtgar, M., Gorospe, M. and Fujita, Y.
Abstract:During tumor development, cells acquire multiple phenotypic changes upon misregulation of oncoproteins and tumor suppressor proteins. Hakai was originally identified as an E3 ubiquitin-ligase for the E-cadherin complex that regulates cell-cell contacts. Here, we present evidence that Hakai plays a crucial role in various cellular processes and tumorgenesis. Overexpression of Hakai affects not only cell-cell contacts, but also proliferation in both epithelial and fibroblast cells. Furthermore, the knockdown of Hakai significantly suppresses proliferation of transformed epithelial cells. Expression of Hakai is correlated to the proliferation rate in human tissues, and is highly up-regulated in human colon and gastric adenocarcinomas. Moreover, we identify PSF, a RNA-binding protein, as a novel Hakai-interacting protein. By using cDNA arrays, we have determined various specific PSF-associated mRNAs encoding proteins that are involved in several cancer-related processes. Hakai affects the ability of PSF to bind these mRNAs, and expression of PSF shRNA or a dominant negative PSF mutant significantly suppresses proliferation of Hakai-overexpressing cells. Collectively, these results suggest that Hakai is an important regulator of cell proliferation and that Hakai may be an oncoprotein and a potential molecular target for cancer treatment.
Keywords:Cadherins, Cell Adhesion, Cell Line, Cell Proliferation, Endometrium, Flow Cytometry, Fluorescent Antibody Technique, Immunohistochemistry, Lymph Nodes, Messenger RNA, Mutation, NIH 3T3 Cells, Neoplasms, Oligonucleotide Array Sequence Analysis, Protein Binding, RNA Interference, RNA-Binding Proteins, Tumor Cell Line, Ubiquitin-Protein Ligases, Western Blotting, Animals, Animals
Source:Molecular Biology of the Cell
Publisher:American Society for Cell Biology
Page Range:3533-3542
Date:August 2009
Additional Information:Copyright (c) 2009 by The American Society for Cell Biology
Official Publication:https://doi.org/10.1091/mbc.E08-08-0845
PubMed:View item in PubMed

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