Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells
Abstract
Cancer stem cells (CSCs), a cell population with acquired perpetuating self-renewal properties that resemble normal stem cells, specifically in the ability to infinitely give rise to the bulk of a tumor as the "seed" of the cancer, account for cancer initiation, progression, recurrence, and chemoresistance. To date, treatment strategies designed to eliminate CSCs still remain a significant challenge, and delineation of the underlying mechanism(s) sustaining a self-renewing CSC pool likely holds the key to the development of effective treatments that can eradicate the genesis of the cancer. Notably, during the CSC division, at least one of the two daughter cells would have to inherit the self-renewal properties in order to maintain the CSC pool. Understanding how the decision is made to retain CSC cell fate or otherwise to undergo differentiation (loss of self-renewal properties) is key to targeting CSCs. However, the critical components and mechanisms involved in the regulation of the CSC fate decision still remain largely unknown. Therefore, the project aims to elucidate such mechanisms that can be therapeutically targeted to direct the differentiation of breast CSCs. Our preliminary data reveal that lost expression/activity of a protein involved in control of cell orientation, Protein Kinase C zeta (PKCzeta), is able to switch the CSC cell fate towards differentiation. This newly identified mechanism will provide important therapeutic implications for the discovery of new anti-cancer drugs (e.g., PKCzeta inhibitor) that can exhaust CSCs to eradicate breast cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510644
Entities
People
- Chun-ju Chang
Organizations
- United States Army
- University of Virginia