Mutations affect gene functions related to cancer behavior including cell growth, metastasis, and drug responses. By analyzing pharmacogenomic profiles, we predicted and demonstrated that EPHB6 mutation induce paclitaxel resistance in lung cancer, melanoma, and liver cancer cells. We also found that conformational change of EPHB6 mutant reduced recruitment of c-Cbl, diminishing EPHA2 degradation. Enhanced EPHA2 signaling induced expression of adhesion molecules resulting in acquisition of cell adhesion-mediated drug resistance (CAM-DR). We also report that the paclitaxel resistance was achieved by expression of CDH11 and subsequent activation of RhoA/focal adhesion kinase (FAK). In conclusion, we suggest that EPHB6 mutation induces paclitaxel resistance by activating EPHA2/CDH11/RhoA/FAK signaling axis, which can be a novel diagnostic or therapeutic target for the treatment of cancer patients with paclitaxel resistance.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
Total Visit :10,658,937
Total Download :4,385,663
Today View :2,319
Ajou University Medical Information & Media Center 164 Worldcup-ro Yeongtong-gu Suwon 16499 Korea / TEL : 031-219-5312 Copyright (c) Ajou University Medical Information & Media Center All Rights Reserved. AJOU Open Repository는 국립중앙도서관 OAK 보급사업으로 구축되었습니다.