Targeting TUBG1 in RB1-negative tumors.

ABSTRACT: The disruption of microtubule dynamics serves as a pivotal strategy for eliminating tumor cells, despite its accompanying toxicities affecting non-tumor cells. This study investigates the potential of selectively targeting γ-tubulin1 (TUBG1) as a therapeutic strategy in cancer treatment. By elucidating the TUBG1-E2F1-retinoblastoma protein (RB1) network, we introduce a novel compound, 4-(6-((3-Methoxyphenyl)amino)pyrimidin-4-yl)-N,N-dimethylbenzenamine, (L12). L12 treatment enhanced RB1 expression and selectively targeted cells with impaired RB1 signaling, while reduced E2F1 expression attenuated its cytotoxicity. Furthermore, L12-mediated cytotoxicity depends on an E2F1-mediated upregulation of procaspase 3 expression, highlighting the role of E2F1 in the apoptotic response. Unlike tradit

SUBMITTER: Lindstrom L 

PROVIDER: S-EPMC11869804 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature