Author/Authors :
Swanton، نويسنده , , Charles and Marani، نويسنده , , Michela and Pardo، نويسنده , , Olivier and Warne، نويسنده , , Patricia H. and Kelly، نويسنده , , Gavin and Sahai، نويسنده , , Erik and Elustondo، نويسنده , , Frederic C. Chang، نويسنده , , Jenny and Temple، نويسنده , , Jillian and Ahmed، نويسنده , , Ahmed A. and Brenton، نويسنده , , James D. and Downward، نويسنده , , Julian and Nicke، نويسنده , , Barbara، نويسنده ,
Abstract :
Summary
xic drug resistance is a major cause of cancer treatment failure. We report an RNA interference screen to identify genes influencing sensitivity of different cancer cell types to chemotherapeutic agents. A set of genes whose targeting leads to resistance to paclitaxel is identified, many of which are involved in the spindle assembly checkpoint. Silencing these genes attenuates paclitaxel-induced mitotic arrest and induces polyploidy in the absence of drug. We also identify a ceramide transport protein, COL4A3BP or CERT, whose downregulation sensitizes cancer cells to multiple cytotoxic agents, potentiating endoplasmic reticulum stress. COL4A3BP expression is increased in drug-resistant cell lines and in residual tumor following paclitaxel treatment of ovarian cancer, suggesting that it could be a target for chemotherapy-resistant cancers.
