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| Item Type: | Article |
|---|---|
| Title: | Novel roles of Hakai in cell proliferation and oncogenesis |
| Creators Name: | Figueroa, A. and Kotani, H. and Toda, Y. and Mazan-Mamczarz, K. and Mueller, E.C. and Otto, A. and Disch, L. and Norman, M. and Ramdasi, R. and Keshtgar, M. and 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 |
| ISSN: | 1059-1524 |
| Publisher: | American Society for Cell Biology |
| Volume: | 20 |
| Number: | 15 |
| 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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