Vitamin K-Mediated Carboxylation in Breast Cancer
Abstract
In this project, we will investigate the relevance of a protein modification pathway that has yet to be studied in breast cancer. Studying this pathway is of particular interest because through use of gene expression datasets from human tumors, we determined that the essential genes of this pathway (and their encoded proteins) are expressed in both normal mammary gland and in many breast cancers. Using these same data, we were able to analyze survival of patients whose tumors expressed the genes of this pathway compared to patients whose tumors did not. The data showed that patients with tumors that had high expression of this pathway experienced significantly shorter survival time (90 months) compared to the group with tumors that did not express this pathway (130 months). Together these observations imply that a subset of aggressive breast cancers are dependent on this pathway for survival and that therapies designed to inhibit this pathway could extend survival of patients bearing such tumors. It is particularly notable that vitamin K is an essential cofactor in this pathway, suggesting that vitamin K status may be an important modifying factor for survival in these patients. Furthermore, several Food and Drug Administration-approved drugs that are routinely used in the clinic are known to antagonize this pathway and would be predicted to selectively inhibit the subset of tumors dependent on this pathway. Ours will be the first studies to examine whether vitamin K or vitamin K antagonists impact breast cancer biology. The impacts of this project include (1) demonstration that this pathway is a target for therapy in a subset of breast cancer patients; (2) attention to vitamin K status as breast cancer progression factor; (3) rapid translation via re-purposing existing drugs; (4) potential future development of blood test to track disease activity in this subset of breast cancer patients; and (5) generation of tools for future research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610494
Entities
People
- JoEllen Welsh
Organizations
- State University of New York at Albany
- United States Army