FOXM1-LDHA signaling promoted gastric cancer glycolytic phenotype and progression.
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.
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.
Weihua
W
Jiang
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.
Fei
F
Zhou
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.
Ning
N
Li
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.
Qi
Q
Li
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.
Liwei
L
Wang
D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D004789:Enzyme Activation; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation
C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5
FOXM1; LDHA; gastric cancer; glycolysis1; progression