Notch signaling is highly conserved in evolution, which plays critical role in organisms’ development. In mammalian, there are four Notch receptors, Notch1 to 4, There are three domains in Notch receptors, including functional extracellular (NECD), transmembrane (TM) and intracellular (NICD). Five Notch ligands, Jagged-1, Jagged-2, Delta-like-1 (DLL1), Delta-like-3 (DLL3) and Delta-like-4 (DLL4) had been identified [
27,
28]. Both the Notch ligands and the receptors are transmembrane proteins. When ligands bind receptors, Notch receptors become susceptible to proteolytic cleavage mediated by secretase complex, which releases the intracellular domain of Notch. NICD enters nucleus and forms a complex with recombination signal binding protein-Jk, which contains a DNA binding domain. The complex regulates Myc, P21, HES family, Cyclin D3 and other Notch target genes. The deregulation of Notch signaling has been proved to be related to several cancers [
27]. Studies showed that DLL4, Jagged-1, Notch1 and Notch4 were highly expressed in KGN cells (FOXL2-mutated granulosa tumor cell line), compared with granulosa-lutein cells. DAPT, an inhibitor of γ-secretase, was used to treat KGN cells and the inhibition of Notch system lead to lower proliferation and viability, as well as estradiol and progesterone secretion of KGN cells [
13,
29]. Several apoptotic parameters such as BAX, BCLXs, PARP and caspase eight cleavages were increased after DAPT treatment. The interaction of Notch signaling and PI3K/AKT signaling were also been proved in the process. AKT phosphorylation was decreased and PTEN (phosphatase and tensin homolog deleted on chromosome ten) protein was increased after Notch signaling inhibition [
13]. More studies are needed to demonstrate that Notch signaling would be potential therapeutic targets for AGCT.