Interaction between granulin A and enolase 1 attenuates the migration and invasion of human hepatoma cells

Abstract

Granulin A (GRN A), a peptide with a molecular 6 kDa, is derived from proteolysis of progranulin (PGRN). Previous study in our laboratory has shown that GRN A is able to inhibit cancer cell growth significantly. In the present study, we confirmed that GRN A can bind to α-enolase (ENO1) specifically as analyzed using Pull-down/MS approaches. The interaction of GRN A with ENO1 was further confirmed by Western blotting and Surface plasmon resonance (SPR) analysis. Treatment of human HepG-2 cells with GRN A inhibited cancer cell growth as well as migration and invasion of cancer cells as analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) and Scratch wound healing assay as well as Transwell experiments. Additionally, GRN A treatment results in augmentation of glucose uptake in cancer cells. Further study reveals that higher expression of ENO1 reversed the inhibitory effects of GRN A on migration and invasion of HepG-2 cells. The increase of glucose uptake, as well as the expression of apoptosis-related genes, is also reversed in cells overexpressing ENO1. The study provides solid evidence that there is the interaction between GRN A and ENO1 and the interaction is responsible for the effects of GRN A on glucose uptake as well as cancer cell migration and invasion.