Here, we hypothesize that aPKCs are essential for NB progression while 14-3-3 and Smad2/3 play central roles by coordinating aPKCs in the cell cycle (via the aPKC/Cdk7/Cdk2 pathway) and cancer progression via Akt1/NFκB/TGF-β pathways. Here, SMAD2 is linked to neuroblastoma.