Restoration of FBP1 suppressed Snail-induced epithelial to mesenchymal transition in hepatocellular carcinoma

Gao-Min Liu,Wen-Jie Hu,Qiao Li,Bin Chen,Bao-Gang Peng,Peng-Fei Zhang,Wen-Xuan Xie,Shun-Li Shen,Jian Wu,Xiao-Yong Huang

doi:10.1038/s41419-018-1165-x

Abstract

Fructose-1,6-bisphosphatase (FBP1), one of the rate-limiting gluconeogenic enzymes, plays critical roles in several cancers and is treated as a tumour suppressor. However, its role in hepatocellular carcinoma (HCC) is unclear. Here, we demonstrated that FBP1 was significantly inhibited during Snail-induced epithelial to mesenchymal transition (EMT) and tissues in HCC. Restoration of FBP1 expression in HCC cancer cells suppressed EMT phenotype, tumour migration and tumour growth induced by Snail overexpression in SMMC-7721 cells. Gene set enrichment analyses revealed significantly enriched terms, including WNT, Notch, ESC, CSR and PDGF, in the group with high Snail and low FBP1 compared with those with low Snail and high FBP1. Low FBP1 expression was significantly correlated with higher AFP level, satellite nodules, portal vein tumour thrombus, and advanced tumour stage. Survival analyses showed that FBP1 was an independent prognostic factor for overall survival and recurrence-free survival. In conclusion, our study revealed a vital role for FBP1 in Snail-induced EMT and prognostic prediction in HCC.

Highlights

Hepatocellular carcinoma (HCC) remains a global public health issue
FBP1 was suppressed during Snail-induced epithelial to mesenchymal transition (EMT) We first examined the expression of Snail using qRT
We transfected SMMC-7721 cells with a Snail overexpression plasmid to enhance the expression of Snail (SMMC-7721-Snail cells) (Fig. 1b, h)

Summary

Introduction

Hepatocellular carcinoma (HCC) remains a global public health issue. It is ranked as the fifth leading cancer and the second leading cause of cancer-related mortality[1]. The ability of differentiated epithelial cells to acquire mesenchymal traits during embryonic development, wound healing, malignant tumour progression and Glucose homeostasis is reciprocally controlled by the catabolic glycolysis/oxidative phosphorylation (OXPHOS) and the anabolic gluconeogenesis pathway. Aberrant glucose metabolism promotes tumourigenesis and progression in many cancers[6]. As first described in 1920s, some tumour cells preferentially rely on glycolysis rather than OXPHOS, even in conditions with ample oxygen (“aerobic glycolysis” or “Warburg effect”)[7]. While previous studies have paid much attention to abnormal glycolysis, little effort has been made to understand the role of gluconeogenesis, the reciprocal metabolic process of glycolysis, in cancer. Fructose-1,6-bisphosphatase (FBP1), Official journal of the Cell Death Differentiation Association

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