Small molecule intervention of actin-binding protein profilin1 reduces tumor angiogenesis in renal cell carcinoma.

ABSTRACT: Angiogenesis plays a key role in the development and progression of renal cell carcinoma (RCC). Actin-binding protein profilin1 (Pfn1) is overexpressed in clear cell RCC predominantly in tumor-associated vascular endothelial cells (ECs). We previously demonstrated that EC-selective (over)expression of Pfn1 accelerates RCC progression, and conversely, genetic loss of EC-Pfn1 dramatically inhibits tumor angiogenesis impeding tumor initiation and/or progression in RCC, suggesting that Pfn1 could be an actionable therapeutic target in RCC. In this study, we demonstrate that 4,4'-((4-bromophenyl)methylene)bis(3,5-dimethyl-1H-pyrazole), a small molecule that we had previously identified as an inhibitor of Pfn1-actin interaction, directly binds to Pfn1 and attenuates tumor angiogenesis when direc

SUBMITTER: Gau D 

PROVIDER: S-EPMC12805099 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature