Integrin Regulation of Ferroptosis in Breast Cancer
Abstract
The hypothesis being tested in this proposal is that breast cancer cells, especially metastatic cells, are prone to rapid increases in ROS and lipid peroxidation caused by adverse micro-environmental conditions and that these oxidative bursts could have deleterious consequences including ferroptosis. Ferroptosis is defined as an iron-dependent, non-apoptotic form of programmed cell death characterized by the accumulation of intracellular soluble and lipid reactive oxygen species (ROS). For this reason, breast tumor cells must acquire mechanisms to protect against oxidative bursts and ferroptosis to metastasize. Work accomplished during the first year of this proposal has demonstrated that the a6b4 integrin protects breast tumor cells against ferroptosis caused by drugs that induce this form of cell death, as well as by detachment from the extracellular matrix. The work performed also revealed that the mechanism involves the ability of a6b4 integrin signaling to sustain expression of glutathione peroxidase 4 (GPX4), an enzyme that reduces lipid peroxides and promotes resistance to ferroptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2008
- Accession Number
- AD1050574
Entities
People
- Arthur M Mercurio
Organizations
- University of Massachusetts Medical School