Critical Role of Protein Condensation in Breast Cancer
Abstract
The proposed research will address the Overarching Challenge of identifying what drives breast cancer growth and determining how to stop it. The successful growth of breast cancer cells requires the cells to orchestrate the expression of many proteins to support the high demand of cell division and to overcome the hostile response that a normal cell has evolved to protect itself from becoming a cancer cell. As a result, breast cancer cells become “addicted” to some of these proteins in order to grow, and inactivating these proteins can significantly inhibit the growth of breast cancer cells. This proposal will study such a protein that we found to be required for breast cancer cell growth but not essential for normal cell or normal animal physiology. This key feature makes this protein a potential target in treatment of breast cancer as the toxicity is likely to be very low. Our preliminary data indicate that this protein has a striking feature of forming liquid-like droplets in cells and that this property appears to mediate its activity in promoting tumor formation. The objective of this proposal is to determine if this novel property of this protein is important in promoting breast cancer in clinically relevant model systems and also to learn some of the underlying mechanisms. If successfully accomplished, our proposed research will provide an entirely new avenue of treating breast cancer, that is, we may be able to inhibit breast cancer by disrupting or solidifying the droplet formation of a key regulator. Our research will particularly benefit patients of triple-negative breast cancer, which is negative for estrogen receptors, progesterone receptors, and excess HER2 protein, and is a very aggressive type of breast cancer with a poor prognosis. As our research expands in the future, other types of breast cancer may also ultimately benefit from the knowledge learned from our project. As it is in the proof-of-concept stage, it will take a number of years to achieve patient-related outcomes, but the interim outcomes will be establishment of a fundamentally new property that fuels breast cancer growth. This will likely make a leap forward toward the Breast Cancer Research Program’s mission of ending breast cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010020
Entities
People
- Hao Jiang
Organizations
- United States Army
- University of Virginia