Rack1 mediates Src binding to drug transporter P-glycoprotein and modulates its activity through regulating Caveolin-1 phosphorylation in breast cancer cells

• DOI: 10.1038/s41419-019-1633-y
• Publication Date: 2019-05-21T11:06:56Z
• Authors: Yanling Fan; Weiyao Si; Wei Ji; Zhiyong Wang; Zicong Gao; Ran Tian; Weijie Song; He Zhang; Ruifang Niu; Fei Zhang
• Keywords: P-glycoprotein; Lipid raft; Caveolin 1

Abstract The failure of chemotherapy and the emergence multidrug resistance (MDR) are major obstacles for effective therapy in locally advanced metastatic breast cancer. Overexpression drug transporter P-glycoprotein (P-gp) cancer cells is one main causes MDR due to its ability efflux anticancer drugs out cells. Although signaling node that regulates expression P-gp has been intensively investigated; regulatory mechanism underlying transport activity remains obscure. Herein, we reported Rack1 tyrosine kinase Src confer through modulating function without altering protein level. We provide evidences regulate by caveolin-1 (Cav1) phosphorylation. Importantly, acts as a hub mediates binding P-gp, thereby facilitating phosphorylation Cav1 abolishing inhibitory effect on P-gp. Taken together, our results demonstrate pivotal roles drug-resistant Our findings also novel insights into regulating activity. may represent new target development therapies reversing resistance.