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EPHB6 mutation induces cell adhesion-mediated paclitaxel resistance via EPHA2 and CDH11 expression

Authors
Yoon, Sarah | Choi, Ji-Hye | Kim, Sung Joo | Lee, Eun-Ju | Shah, Masaud | Choi, Sangdun | Woo, Hyun Goo
Department
Department of Physiology, Ajou University School of Medicine  | Department of Biomedical Sciences, Graduate School of Ajou University
Abstract
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.
Keywords
Appears in Collections:
Poster > School of Medicine / Graduate School of Medicine > Department of Physiology
Poster > Graduate School of Biomedical Sciences > Biomedical Sciences, The Graduate School
Ajou Authors
대학, 생리학교실  |  대학원, 의생명과학과
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