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 | Tian-Lin He, Yi-Jie Zhang, Hui Jiang, Xiao-Hui Li, Hai Zhu, Kai-Lian Zheng |
| Journal | Medical oncology (Northwood, London, England) (Med Oncol) Vol. 32 Issue 7 Pg. 187 (Jul 2015) ISSN: 1559-131X [Electronic] United States |
| PMID | 26021472 (Publication Type: Journal Article) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!