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

Abstract

Cancer: Gene mutation spurs drug resistance Mutations in a gene linked to cancer growth also underpin resistance to a common chemotherapy drug. Hyun Goo Woo and colleagues from Ajou University in Suwon, South Korea, analyzed a large database of genetic information on more than 1,000 human cancer cell lines looking for mutated genes associated with resistance to certain drugs. The top association was between mutated forms of EPHB6, a gene previously linked to tumor invasiveness, and resistance to paclitaxel, a chemotherapy drug used to treat a range of different cancers. They experimentally validated the finding in lung, skin and liver cancer cell lines. The researchers also identified two proteins activated by mutant EPHB6 that promote the cell adhesion responsible for paclitaxel resistance. Inhibiting these two proteins reversed the drug resistance in cells, suggesting the therapeutic value of targeting this pathway.