Glucose-Dependent FOXM1 Promotes Epithelial-to-Mesenchymal Transition Via Cellular Metabolism and Targeting Snail in Human Pancreatic Cancer. Issue 2 (February 2020)

• Record Type: Journal Article
• Authors: Kyuno, Takuro; Kohno, Takayuki; Konno, Takumi; Yamaguchi, Hiroshi; Kyuno, Daisuke; Imamura, Masafumi; Kimura, Yasutoshi; Kojima, Takashi; Takemasa, Ichiro
• Is Part Of: Pancreas. Volume 49:Issue 2(2020)
• Publication Date: 2020-02
• Subjects: FOXM1 -- EMT -- claudin-1 -- Snail -- cellular metabolism -- cell migration; Pancreas -- Diseases -- Periodicals; Pancreas -- Periodicals; Neuroendocrine tumors -- Periodicals; 616.37005
• DOI: 10.1097/MPA.0000000000001485
• Languages: English
• ISSNs: 0885-3177

Abstract

Abstract : Objectives: Transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in the progression of cancer including epithelial-to-mesenchymal transition (EMT). The aim of this study is to characterize the regulatory mechanisms of FOXM1 in EMT via pancreatic cancer metabolism. Methods: We investigated the regulation of EMT via mitochondrial respiration by FOXM1 using pancreatic cancer cell lines HPAC and PANC-1 and normal human pancreatic duct epithelial cells. Results: Forkhead box protein M1 and Snail were strongly expressed in HPAC and PANC-1. Epithelial-to-mesenchymal transition–modulated claudin-1 level was lower in PANC-1 than in HPAC. In both cell lines in low-glucose medium, FOXM1 and Snail were decreased and claudin-1 was increased. Knockdown of FOXM1 increased claudin-1 and decreased Snail in both cell lines. Low-glucose medium and downregulation of FOXM1 inhibited the cell migration in both cell lines. In both cell lines, mitochondrial respiration was at higher levels in low-glucose medium than in high-glucose medium. Downregulation of FOXM1 induced mitochondrial respiration in high-glucose medium. In normal human pancreatic duct epithelial cells, FOXM1 and Snail were low and claudin-1 was highly expressed, whereas overexpression of FOXM1 decreased claudin-1. Conclusions: Glucose-dependent FOXM1 promoted EMT via Snail and pancreatic cancer metabolism.