Authors:
C Swanton, M Marani, O Pardo, PH Warne, G Kelly, E Sahai, F Elustondo, J Chang, J Temple, AA Ahmed, JD Brenton, J Downward, B Nicke
Journal name: 
Cancer Cell
Citation info: 
11(6):498-512
Abstract: 
Cytotoxic 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.
DOI: 
http://doi.org/10.1016/j.ccr.2007.04.011
Research group: 
Brenton Group
E-pub date: 
01 Jun 2007