Define the Twist-ATX-LPAR1 Signaling Axis in Promoting Obesity-Associated Triple Negative Breast Cancer
Abstract
Breast cancer remains the second leading cause of cancer-related death in women worldwide. Triple negative breast cancer (TNBC) carries a poorer prognosis compared to other subtypes of breast cancer, given its higher genomic instability, tendency toward early metastasis, and lack of effective targeted therapies. As obesity is a risk factor for TNBC, understanding the mechanistic linkage between TNBC and obesity is crucial for the development of novel prevention and treatment strategies. TNBC activates the epithelial-mesenchymal transition (EMT) program mediated by EMT transcription factors, including Twist. Twist is highly expressed in TNBC cells, and its expression is positively correlated with metastatic potential. Our preliminary data showed that Twist interacted with BRD4 to regulate its target gene transcription, and Autotaxin (ATX) and LPAR1 were dramatically increased in Twist-overexpressing breast cancer cells and adipocytes. Encoded by the ENPP2 gene, ATX is a secreted enzyme that produces most of the extracellular lysophosphatidic acid (LPA), which signals through its receptors (LPAR1-6) to mediate a wide range of inflammatory processes including wound healing, fibrosis and metastasis. Interestingly, both Twist and ATX were demonstrated to be involved in diet-induced obesity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2020
- Accession Number
- AD1119016
Entities
People
- Yiwei Lin
Organizations
- University of Kentucky