Abstract
The proto-oncogene pp60c-Src (c-Src) is activated in many types of cancer and contributes to the transformed phenotype of the tumor, although its role is not yet fully understood. Here we report that active Src elevates the levels of β-catenin by enhancing cap-dependent translation. Src induces phosphorylation of the eukaryotic initiation factor 4E via the Ras/Raf/ERK pathway and the phosphorylation of its inhibitor 4E-BP1 via the PI3K/mTOR pathway. Activated Src enhances the accumulation of nuclear β-catenin and enhances its transcriptional activity, elevating target genes such as cyclin D1. This novel activation of the Wnt pathway by Src most probably contributes to the oncogenic phenotype of cancer cells.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://mcb.asm.org/.
ACKNOWLEDGMENTS
We thank Eli Keshet for fruitful discussions and reagents; Yinon Ben-Neria (Haddasah Medical School, The Hebrew University of Jerusalem) for the Myc-β-catenin, HA-IκBα, Flag-Axin, and HA-GSK3 plasmids; and Nahum Sonenberg (McGill University, Montreal, Quebec, Canada) for eIF4E and 4EBP1 expression plasmids.
This study was partially supported by a grant from the Israel Science Foundation (ISF), Jerusalem, Israel.