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.
Original language | English (US) |
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Pages (from-to) | 498-512 |
Number of pages | 15 |
Journal | Cancer Cell |
Volume | 11 |
Issue number | 6 |
DOIs | |
State | Published - Jun 12 2007 |
Keywords
- CELLCYCLE
- CHEMBIO
ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Oncology