Down-regulation of FBP1 in lung adenocarcinoma cells promotes proliferation and invasion through SLUG mediated epithelial mesenchymal transformation

Abstract

Background: Metabolic reprogramming and epithelial-mesenchymal transformation (EMT) play an important role in lung cancer. In recent studies, metabolic enzymes such as Fructose-1,6-bisphosphatase 1 (FBP1) have shown potential functions beyond regulating metabolism.Methods: Western blot assay was performed to detect glycolysis-related and EMT-related protein expression levels. The glucose uptake kit and adenosine triphosphate (ATP) detection kit were used to detect glucose uptake rate and ATP content. Transwell assay was used to determine the invasiveness of lung adenocarcinoma cells. Wound healing assay was used to determine the metastatic ability of lung adenocarcinoma cells. Methyl thiazolyl tetrazolium (MTT) assay and EdU staining were performed to investigate the effect of FBP1 overexpression on lung adenocarcinoma proliferation.Results: Overexpression of FBP1 down-regulated glycolysis-related protein levels and inhibited glucose uptake and ATP production, while knockdown of FBP1 had the opposite effect. Overexpression of FBP1 reversed EMT and inhibited Slug expression. Meanwhile, overexpression of FBP1 impaired the invasion, metastasis and proliferation ability of lung adenocarcinoma cells. In contrast, FBP1 knockdown promoted the EMT process, up-regulated Slug expression and enhanced the invasion, metastasis and proliferation of lung adenocarcinoma cells.Conclusions: Therefore, FBP1 can be used as one of the potential clinical targets through inhibiting glycolysis, cell invasion and proliferation by inhibiting Slug mediated EMT processes.

FBP1 inhibits NSCLC stemness by promoting ubiquitination of Notch1 intracellular domain and accelerating degradation

“…Our previous investigation confirmed the down-regulation of FBP1 in lung adenocarcinoma, where it functioned as a tumor suppressor by inhibiting proliferation and epithelial–mesenchymal transition (EMT) in lung adenocarcinoma cells [ 31 ]. Accumulating research findings support a direct association between EMT and the preservation of cancer stem cell (CSC) characteristics [ 32 – 36 ].…”

In-depth single-cell and bulk-RNA sequencing developed a NETosis-related gene signature affects non-small-cell lung cancer prognosis and tumor microenvironment: results from over 3,000 patients

“…Some of these genes have been extensively studied in relation to LUAD. Overexpression of ALDH2 (protective factor in our study) decreased migration, and proliferation in LUAD cells, but knockdown of ALDH2 increased these properties ( 34 ); the growth rate of lung cancer cells overexpressed with CKAP4 (risk factor in our study) was increased in vivo , while an antibody against the protein inhibited it ( 35 ); LUAD cells were impaired in their ability to invade, metastasize, and proliferate after FBP1 (protective factor in our study) was overexpressed ( 36 ); FKBP4 and S100P (risk factors in our study) promotes proliferation and migration of NSCLC cells and inhibits apoptosis, while promoting tumor growth in vivo ( 37 , 38 ). Additionally, GO and GSVA enrichment analyses showed that genes positively associated with NETRS were significantly enriched in functions related to cell cycle.…”

Exploring the Functions of Mutant p53 through TP53 Knockout in HaCaT Keratinocytes

“…MAGED1 repression is a characteristic of tumor cells. Likewise, the expression of FBP1, which acts as a rate-limiting enzyme in gluconeogenesis, is commonly reduced in tumor cells [43]. In TP53-KO cells, FBP1 expression was markedly reduced (log2FC = −5.32).…”