title: The c-Myc-LDHA axis positively regulates aerobic glycolysis and promotes tumor progression in pancreatic cancer.
abstract: The transcription factor c-Myc plays critical roles in cancer development and progression through regulating expression of targeted genes. Lactate dehydrogenase A (LDHA), which catalyzes the conversion of L-lactate to pyruvate in the final step of anaerobic glycolysis, is frequently upregulated in pancreatic cancer. However, little is known about the effects of c-Myc-LDHA axis in the progression of pancreatic cancer. In this study, we found that c-Myc and LDHA are concomitantly overexpressed in pancreatic cancer cell lines and clinical specimens. c-Myc overexpression and LDHA overexpression were correlated with TNM stage and tumor size and indicated poor prognosis in patients with pancreatic cancer. Knockdown of c-Myc reduced the protein expression of LDHA, lactate production and glucose consumption, and silencing of LDHA mimicked this effect. Meanwhile, reduced c-Myc-LDHA signaling resulted in decreased tumor growth and metastasis in pancreatic cancer. Treatment with 2-Deoxy-D-glucose, an inhibitor of anaerobic glycolysis, completely blocked the oncogenic roles of c-Myc-LDHA signaling. Taken together, dysregulated c-Myc-LDHA signaling plays important roles in aerobic glycolysis and facilitates tumor progression of pancreatic cancer.
authors.affiliation: Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, 168#, Changhai Road, Shanghai, 200433, China.
authors.forename: Tian-Lin
authors.initials: TL
authors.lastname: He
authors.forename: Yi-Jie
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
authors.forename: Hai
authors.initials: H
authors.lastname: Zhu
authors.forename: Kai-Lian
authors.initials: KL
authors.lastname: Zheng
mesh_terms: D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D005947:Glucose / Q000235:genetics; D006019:Glycolysis / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000235:genetics*; D000080864:Lactate Dehydrogenase 5; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D007527:Isoenzymes; D016271:Proto-Oncogene Proteins c-myc; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D005947:Glucose