Phytic acid inhibits RafGOFScrib−/− tumor growth and invasion by suppressing the Yki-mediated JAK/STAT pathway in Drosophila melanogaster

Abstract

Metastasis is one of the most important factors related to malignant tumor development and therapeutic failure. Phytic acid (PA), a poly-phosphorylated inositol derivative in plant seeds and grains, has been shown to have antitumoral activity. However, the effect of PA on tumor metastasis and the underlying mechanisms remain uncharacterized. In the current study, we aimed to identify the effect of PA on tumor metastasis by employing a Drosophila model of malignant tumor RafGOFScrib−/−. We observed that PA supplementation in food inhibited the invasion and migration of tumors. Further studies indicated that PA drives Yki phosphorylation and inactivation through Lats kinase, which subsequently results in decreased expression of the JAK/STAT pathway ligands unpaired cytokines (Upds). Moreover, the reduced JAK/STAT pathway inhibits the recruitment and proliferation of hemocytes. To summarize, these findings provide valuable pathological and mechanistic insights into the potential application of PA for functional food or natural medicine development.