ABSTRACT
In cancer, suppression of protein phosphatases, such as protein phosphatase 2A (PP2A), that normally counteract kinases, contributes to aberrant signaling. Leonard et al. recently demonstrated that a novel small-molecule activator of PP2A, DT-061, selectively stabilizes a specific PP2A holoenzyme responsible for dephosphorylating critical oncogenic targets, including MYC. The 3.6-Å cryo-electron microscopy map of the heterotrimer assembly provides insight into the druggable structure of PP2A, guiding future phosphatase therapeutics.
Subject(s)
Neoplasms , Protein Phosphatase 2 , Cryoelectron Microscopy , Humans , Neoplasms/drug therapy , Protein Phosphatase 2/metabolism , Signal TransductionABSTRACT
In this issue of Cancer Discovery, Sodir and colleagues employ a pancreatic ductal adenocarcinoma mouse model with mutant KRAS and inducible MYC to demonstrate that MYC acts as a reversible driver of malignant tumor progression. Abrogation of MYC triggers rapid regression and disassembly of the ensemble tumor through both cancer cell-intrinsic and cancer cell-extrinsic mechanisms, providing a compelling rationale for therapeutic targeting of MYC.See related article by Sodir et al., p. 588.