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.

Development of a novel immune-related genes prognostic signature for osteosarcoma

“…CORT is an endogenous cyclic neuropeptide that can regulate the growth and metastasis of lung cancer and thyroid cancer 58 , 59 , and it also regulates the inflammatory response by inhibiting the immune infiltration 60 . Granulin a (GRNA) is a 6 kDa peptide hydrolyzed from PGRN, which can effectively inhibit the growth and invasion of human hepatoma cells 61 . The high expression of VAV1 is a positive prognostic factor for early invasive breast cancer 62 .…”

Alpha-enolase regulates the malignant phenotype of pulmonary artery smooth muscle cells via the AMPK-Akt pathway

“…Although the inhibition of metabolic activity by ENOblock is consistent throughout the literature, the exact mechanism of action of ENOblock in vivo may be complex and not fully understood and even controversial 53 . Some studies support the direct inhibition of ENO by ENOblock 54 , 55 , whereas other researchers argue that such effects may be caused by mechanisms other than direct inhibition of ENO activity 56 . We show that ENOblock can inhibit ENO activity both in vitro and in vivo (supplementary Fig.…”

Unlikely role of glycolytic enzyme ��-enolase in cancer metastasis and its potential as a prognostic biomarker

“…Overexpression of a-enolase has been shown to increase the migration and invasion of hepatocellular carcinoma, colorectal and gastric cancer cells in vitro [11,58,60,61,67] and to enhance colorectal cancer metastasis in vivo [11] , demonstrating that it is an important driver of metastasis in multiple cancer types [ Table 3]. Conversely, knockdown or pharmacological inhibition of a-enolase decreased the migration and invasion of glioma, colorectal, pancreatic and endometrial carcinoma in vitro [6,12,63,68,69] , and decreased tumourigenesis and metastasis of endometrial carcinoma in vivo [12] .…”