The oncogenic transcription factor forkhead box protein M1 (FOXM1) plays critical roles in gastric cancer (GC) development and progression. However, the underlying mechanisms has not fully demonstrated. Lactate dehydrogenase A (LDHA) is widely overexpressed in a series of cancers and is one of the two subunits of Lactate dehydrogenase (LDH), which is the key glycolytic enzyme and catalyzes the interconversion of pyruvate and lactate. In this study, we characterized the regulation of aerobic glycolysis by FOXM1 via transactivation of LDHA in GC. We found that LDHA was overexpressed GC cells, and the expression of LDHA was transcriptionally regulated by FOXM1. Furthermore, FOXM1 regulated GC cells glycolytic phenotype, proliferation, migration and invasion via LDHA. Thus, FOXM1-LDHA signaling functioned as a stimulator of glycolysis and promoted GC progression.
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FOXM1-LDHA signaling promoted gastric cancer glycolytic phenotype and progression.
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Department of Oncology and Shanghai Key Laboratory of Pancreatic Diseases, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital Shanghai, People's Republic of China.
The oncogenic transcription factor forkhead box protein M1 (FOXM1) plays critical roles in gastric cancer (GC) development and progression. However, the underlying mechanisms has not fully demonstrated. Lactate dehydrogenase A (LDHA) is widely overexpressed in a series of cancers and is one of the two subunits of Lactate dehydrogenase (LDH), which is the key glycolytic enzyme and catalyzes the interconversion of pyruvate and lactate.
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Authors' Affiliations: Shanghai Key Laboratory of Pancreatic Diseases Research; Department of Oncology, Shanghai Jiaotong University Affiliated First People's Hospital; Department of General Surgery, Shanghai Jiaotong University Affiliated Ruijin Hospital; Department of Oncology and Tumor Institute, Shanghai East Hospital, Tongji University School of Medicine, Shanghai; Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Pathology Department of Affiliated Hospital, Hainan Medical College, Haikou, People's Republic of China; Departments of Gastroenterology, Hepatology, and Nutrition; and Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
Purpose: The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression. However, the regulatory role and underlying mechanisms of FOXM1 in cancer metabolism are unknown. In this study, we characterized the regulation of aerobic glycolysis by FOXM1 and its impact on pancreatic cancer metabolism.
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