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

The failure of chemotherapy and the emergence of multidrug resistance (MDR) are the major obstacles for effective therapy in locally advanced and metastatic breast cancer. Overexpression of the drug transporter P-glycoprotein (P-gp) in cancer cells is one of the main causes of MDR due to its ability to efflux anticancer drugs out of cells. Although the signaling node that regulates the expression of P-gp has been intensively investigated; the regulatory mechanism underlying P-gp transport activity remains obscure.

Rack1 mediates tyrosine phosphorylation of Anxa2 by Src and promotes invasion and metastasis in drug-resistant breast cancer cells.

Background: Acquirement of resistance is always associated with a highly aggressive phenotype of tumor cells. Recent studies have revealed that Annexin A2 (Anxa2) is a key protein that links drug resistance and cancer metastasis. A high level of Anxa2 in cancer tissues is correlated to a highly aggressive phenotype.