High-Frequency Canonical Wnt Activation in Multiple Sarcoma Subtypes Drives Proliferation through a TCF/β-Catenin Target Gene, CDC25A
| Autor: | Yan Chen, Luca Grumolato, Stuart A. Aaronson, Guizhong Liu, Gal Akiri, Shen Yao, Sapna Vijayakumar, Ioana A. Rus |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
0303 health sciences
Cancer Research Beta-catenin biology Adenomatous polyposis coli Wnt signaling pathway LRP6 LRP5 Cell Biology TCF/LEF family 3. Good health 03 medical and health sciences 0302 clinical medicine Oncology 030220 oncology & carcinogenesis Catenin biology.protein Cancer research Autocrine signalling 030304 developmental biology |
| Zdroj: | Cancer Cell. 19(5):601-612 |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccr.2011.03.010 |
| Popis: | SummaryWnt canonical signaling is critical for normal development as well as homeostasis of several epithelial tissues, and constitutive activation of this pathway is commonly observed in carcinomas. We show here that 50% of human sarcomas (n = 45) and 65% of sarcoma cell lines (n = 23) of diverse histological subtypes exhibit upregulated autocrine canonical Wnt signaling. Furthermore, in Wnt autocrine cell lines, we identify alterations including overexpression or gene amplification of Wnt ligands and/or LRP5/6 coreceptors and epigenetic silencing of different cell surface Wnt antagonists. Mutations in adenomatous polyposis coli (APC) gene were observed in two nonautocrine Wnt-positive sarcoma cell lines. Finally, downregulation of the activated Wnt pathway inhibited sarcoma cell proliferation both in vitro and in vivo by a mechanism involving the downregulation of CDC25A. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|