Metabolic plasticity in heterogeneous pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignant neoplasms. The recognized hallmarks of PDA are regarded to be downstream events of metabolic reprogramming. Because PDA is a heterogeneous disease that is influenced by genetic polymorphisms and changes in the microenvironment, metabolic plasticity is a novel feature of PDA. As intrinsic factors for metabolic plasticity, K-ras activation and mutations in other tumor suppressor genes induce abnormal mitochondrial metabolism and enhance glycolysis, with alterations in glutamine and lipid metabolism. As extrinsic factors, the acidic and oxygen/nutrient-deprived microenvironment also induces cancer cells to reprogram their metabolic pathway and hijack stromal cells (mainly cancer-associated fibroblasts and immunocytes) to communicate, thereby adapting to metabolic stress. Therefore, a better understanding of the metabolic features of PDA will contribute to the development of novel diagnostic and therapeutic strategies.
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Chen
C
Liang
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Yi
Y
Qin
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Bo
B
Zhang
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Shunrong
S
Ji
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Si
S
Shi
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Wenyan
W
Xu
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Jiang
J
Liu
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Jinfeng
J
Xiang
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Dingkong
D
Liang
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Qiangsheng
Q
Hu
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Quanxing
Q
Ni
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Jin
J
Xu
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China. Electronic address: yuxianjun@fudanpci.org.
Xianjun
X
Yu
D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology; D059016:Tumor Microenvironment; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C117307:KRAS protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)
Heterogeneity; Metabolic competition; Metabolic phenotype; Metabolic plasticity; Metabolic symbiosis; Pancreatic cancer