Metabolic Regulation of Ovarian Cancer Cell Death
Abstract
Following treatment with chemotherapeutic agents, responsive ovarian cancer cells undergo apoptotic cell death. Several groups have shown that the apoptotic protease, caspase 2 (C2), is an essential activator of cell death in ovarian cancer cells treated with cisplatin and we have found, by knock-down of C2 in ovarian cancer cells, that C2 is also required for responsiveness to microtubule-perturbing agents such as paclitaxel. Work from our laboratory has demonstrated that C2 is normally controlled by the metabolic status of the cell in that high levels of flux through the pentose phosphate pathway (PPP) prevents activation of C2 . Because ovarian cancers exhibit increased glucose uptake and increased fatty acid synthesis, we hypothesized that susceptibility of ovarian cancers to front-line chemotherapeutic agents, reflect, at least in part, the metabolic status of the cells and, consequently, the phosphorylation state of caspase 2. In this past year, we have found that fatty acid synthesis inhibition kills ovarian cancer cells through the induction of a protein known as REDDI. REDDI induction leads to (and is required for ) caspase 2 activation, leading to death of the cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA570124
Entities
People
- Sally Kornbluth
Organizations
- Duke University