(a, b) PPC1 cells were infected with Ad-GFP, Ad-AC (MOI 50), Ad-shSCR or Ad-shASAH1 (MOI 20) 1 day prior to plating on six-well plates in a total volume of 4?ml soft agar
(a, b) PPC1 cells were infected with Ad-GFP, Ad-AC (MOI 50), Ad-shSCR or Ad-shASAH1 (MOI 20) 1 day prior to plating on six-well plates in a total volume of 4?ml soft agar. prostate tumors, and elevation of phosphorylated Akt in tumor versus patient-matched benign tissue is contingent upon AC elevation. Investigation of the mechanism for AC-induced Akt activation revealed that AC activates Akt through sphingosine kinase 1 (SphK1)-derived generation of S1P. This signaling pathway proceeds through S1P receptor 2 (S1PR2)-dependent stimulation of PI3K. Functionally, AC-overexpressing cells are insensitive to cytotoxic chemotherapy, however, these cells are more susceptible to targeted inhibition of Akt. AC-overexpressing cells proliferate more rapidly than control cells and form more colonies in soft agar; however, these effects are profoundly sensitive to Akt inhibition, demonstrating increased dependence on…