Targeting the Mevalonate Pathway and Its Restorative Feedback Loop in Breast Cancer
Abstract
We have shown that targeting the mevalonate pathway with fluvastatin preferentially induces apoptosis in breast cancer (BrCa) cells that have undergone epithelial-to-mesenchyme transition (EMT), a critical process for the initiation of metastasis. Moreover, we have identified that EMT gene expression is bimodally distributed and is a biomarker of fluvastatin sensitivity. Mechanistically, we have shown that fluvastatin can induce apoptosis by limiting production of an important end-product of the mevalonate pathway essential for protein N-glycosylation associated with EMT. We have also shown that dipyridamole(DP) potentiates fluvastatin-induced apoptosis of BrCa cells by blocking the statin-induced restorative feedback loop. We have also identified additional agents that can potentiate statin-induced BrCa cell death, thereby expanding this class of anti-cancer agents. We have published 3 manuscripts (2 at Cancer Research and Molecular Oncology), have another nearly ready for resubmission to Nature Communications, and have published a review article in Clinical Cancer Research. Thus, we have been highly productive and made advances that are actionable and have potential to immediately impact BrCa patient outcome.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2021
- Accession Number
- AD1160522
Entities
People
- Linda Z Penn
Organizations
- University Health Network