biostudies-literatureAntas PFundação para a Ciência e a TecnologiaInstitut National Du CancerFondation Aix-Marseille Universite24https://www.ebi.ac.uk/biostudies/studies/S-EPMC12910983biostudies-literatureUnknown31(1)Inhibition of the phosphatidylinositol kinase vacuolar protein sorting 34 (VPS34) with the pharmacological compound VPS34-IN1 has a range of effects on the dynamics of endosomes. While VPS34 inhibition has been previously suggested as a potential therapeutic approach for treating certain cancers, our findings indicate that it has minimal cytotoxic effects on the leukemic blastic plasmacytoid dendritic cell neoplasm (BPDCN) CAL-1. However, we also found that VPS34-IN1 interferes with the function of this plasmacytoid dendritic cell (pDC) line, by inhibiting Toll-like receptor (TLR)7 signaling. In contrast, VPS34-IN1 triggers activation of the stimulator of interferon genes (STING) and significantly enhances cellular response to the STING agonist 2'3'-cyclic guanosine monophosphate-adenosineCellular & molecular biology lettersVPS34-IN1 potentiates STING-dependent activation in human CAL-1 cells.PMC12910983(PLBIO17-187)CSISFRH/BD/138336/2018 , COVID/BD/153248/2023, https://doi.org/10.54499/COVID/BD/153248/2023Ferreira BHSu BNal BLeite-Pinheiro FDuarte IFMendes AReverendo MPierre PBarros DGatti ECarvoeiro DArguello RJAntas PAlmeida CRRamalhinho CNarita MMendes LFMachado MDfalseVPS34-IN1 potentiates STING-dependent activation in human CAL-1 cells.Inhibition of the phosphatidylinositol kinase vacuolar protein sorting 34 (VPS34) with the pharmacological compound VPS34-IN1 has a range of effects on the dynamics of endosomes. While VPS34 inhibition has been previously suggested as a potential therapeutic approach for treating certain cancers, our findings indicate that it has minimal cytotoxic effects on the leukemic blastic plasmacytoid dendritic cell neoplasm (BPDCN) CAL-1. However, we also found that VPS34-IN1 interferes with the function of this plasmacytoid dendritic cell (pDC) line, by inhibiting Toll-like receptor (TLR)7 signaling. In contrast, VPS34-IN1 triggers activation of the stimulator of interferon genes (STING) and significantly enhances cellular response to the STING agonist 2'3'-cyclic guanosine monophosphate-adenosine2026-01-01T00:00:00Z2026 Jan2026-07-16T00:46:35.037Z2026-07-09T10:26:21.074ZS-EPMC129109834158064210.1186/s11658-025-00841-4