Sam68 is a druggable vulnerability point in cancer stem cells.

Sam68 (Src associated in mitosis of 68 kDa) is an RNA-binding and multifunctional protein extensively characterized in numerous cellular functions, such as RNA processing, cell cycle regulation, kinase- and growth factor signaling. Recent investigations highlighted Sam68 as a primary target of a class of reverse-turn peptidomimetic drugs, initially developed as inhibitors of Wnt/ß-catenin mediated transcription. Further investigations on such compounds revealed their capacity to selectively eliminate cancer stem cell (CSC) activity upon engaging Sam68. This work highlighted previously unappreciated roles for Sam68 in the maintenance of neoplastic self-renewal and tumor-initiating functions. Here, we discuss the implication of Sam68 in tumorigenesis, where central findings support its contribution to chromatin regulation processes essential to CSCs. We also review advances in CSC-targeting drug discovery aiming to modulate Sam68 cellular distribution and protein-protein interactions. Ultimately, Sam68 constitutes a vulnerability point of CSCs and an attractive therapeutic target to impede neoplastic stemness in human tumors.

Identification of cytidine 2',3'-cyclic monophosphate and uridine 2',3'-cyclic monophosphate in Pseudomonas fluorescens pfo-1 culture.

Cytidine 2',3'-cyclic monophosphate (2',3'-cCMP) and uridine 2',3'-cyclic monophosphate (2',3'-cUMP) were isolated from Pseudomonas fluorescens pfo-1 cell extracts by semi-preparative reverse phase HPLC. The structures of the two compounds were confirmed by NMR and mass spectroscopy against commercially available authentic samples. Concentrations of both intracellular and extracellular 2',3'-cCMP and 2',3'-cUMP were determined. Addition of 2',3'-cCMP and 2',3'-cUMP to P. fluorescens pfo-1 culture did not significantly affect the level of biofilm formation in static liquid cultures.