| First Author | Nakayama S | Year | 2014 |
| Journal | Cancer Res | Volume | 74 |
| Issue | 20 | Pages | 5891-902 |
| PubMed ID | 25164010 | Mgi Jnum | J:216696 |
| Mgi Id | MGI:5609226 | Doi | 10.1158/0008-5472.CAN-14-0184 |
| Citation | Nakayama S, et al. (2014) beta-catenin contributes to lung tumor development induced by EGFR mutations. Cancer Res 74(20):5891-902 |
| abstractText | The discovery of somatic mutations in EGFR and development of EGFR tyrosine kinase inhibitors (TKI) have revolutionized treatment for lung cancer. However, resistance to TKIs emerges in almost all patients and currently no effective treatment is available. Here, we show that beta-catenin is essential for development of EGFR-mutated lung cancers. beta-Catenin was upregulated and activated in EGFR-mutated cells. Mutant EGFR preferentially bound to and tyrosine phosphorylated beta-catenin, leading to an increase in beta-catenin-mediated transactivation, particularly in cells harboring the gefitinib/erlotinib-resistant gatekeeper EGFR-T790M mutation. Pharmacologic inhibition of beta-catenin suppressed EGFR-L858R-T790M mutated lung tumor growth, and genetic deletion of the beta-catenin gene dramatically reduced lung tumor formation in EGFR-L858R-T790M transgenic mice. These data suggest that beta-catenin plays an essential role in lung tumorigenesis and that targeting the beta-catenin pathway may provide novel strategies to prevent lung cancer development or overcome resistance to EGFR TKIs. |
