Identifying the Molecular Mechanisms Underlying HIF2-Independent Tumorigenesis in RCC
Abstract
Inactivation of pVHL in ccRCC leads to accumulation of HIF and activation of pathways that play key roles in tumor development, includinginduction of angiogenesis and cell proliferation, regulation of apoptosis and altered metabolism. hOWEVER, not all tumors are sensitive toinhibition of HIF-2 indicating that only some ccRCC tumors are HIF-2 dependent (with 40-60% of patients failing to show disease controlupon treatment). While the oncogenic role of HIF-2 in a subset of ccRCC tumors is well established, the exact role of HIF-1 in tumordevelopment has remained elusive. Here, we study the role of HIF-1 in a novel context that has not been previously possible. In addition, theprecise role of non-canincal targets of VHL including ZHX2 and SFMBT1 in ccRCC are not well understood. Here, we used state of the artPDX lines that have previously been established as HIF2-independent lines, evaluate the role of HIF1A in tumor growth in these lines,examine expression of ZHX2 and SFMBT1, and pinpoint unidentified novel VHL targets.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2022
- Accession Number
- AD1192631
Entities
People
- Faeze Saatchi
Organizations
- University of Texas at Dallas