GenomeRNAi - a database for RNAi phenotypes and reagents
TitleScreen TitleAssayBiomodelSpecies
Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs. Swanton et al. (2007) Anticancer drug enhancers Cell viabilityA549 (lung adenocarcinoma), HCT116 (colon cancer), MDA-MB-231 (breast cancer)H. sapiens


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.

Screen details

Stable Id: GR00113-A-0
Screen title: Anticancer drug enhancers
Assay: Cell viability
Method: ATP levels
Screen type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: A549 (lung adenocarcinoma), HCT116 (colon cancer), MDA-MB-231 (breast cancer)
Library: , Dharmacon (kinases)
Reagent type: siRNA
Score type: np
Cutoff: Significant effect in at least 2 of 3 cell lines