ARIH1 Function in EMT and Tumorigenesis
Abstract
A major obstacle to improving breast cancer care is the effective treatment of breast cancer that has spread to distant sites. Metastatic disease has a dismal 5-year survival rate of 28% across all breast cancer subtypes and only 11% in triple-negative breast cancer (TNBC). A critical barrier in tackling this issue is our lack of understanding of the underlying mechanisms that lead to cancer cells becoming metastatic. We aim to address these important challenges in the treatment of breast cancer, addressing the Breast Cancer Research Program’s (BCRP s) overarching challenges of what drives breast cancer growth and why a subset of breast cancer cells become metastatic. Our laboratory focuses on characterizing the underlying mechanisms contributing to the epithelial to mesenchymal transition (EMT) that is activated in cancer and is thought to facilitate metastasis to distant organs. We recently identified a novel role for the protein ARIH1 in this process, and our research suggests that ARIH1 plays an important role in tumor initiation and metastasis. We see that ARIH1 is upregulated in breast cancer and reducing ARIH1 leads to loss of EMT induction in mammary cells and loss of tumor formation and metastatic spread in TNBC cells. Thus, the proposed aims will address the BCRP’s overarching challenges by characterizing the function and regulation of ARIH1 in breast cancer. In addition, we aim to generate novel ARIH1 inhibitors to test in our breast cancer cells and mouse models. Data from this study will provide a foundation for researchers to develop ARIH1 therapeutics in breast cancer, which addresses the need for novel treatment regimens that are more effective, less toxic, and positively impact survival. Overall, we believe the proposed studies will positively impact cancer patient care in the future.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210706
Entities
People
- Philip H Howe
Organizations
- Medical University of South Carolina
- United States Army