title: Oncogenic KRAS Targets MUC16/CA125 in Pancreatic Ductal Adenocarcinoma.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with the 5-year survival rate less than 6%. Previous results indicated that serum levels of CA125 (encoded by MUC16) could be used to predict which groups of pancreatic cancer patients may benefit from surgery. However, the underlying mechanism remains elusive. Herein, using the Cancer Genome Atlas and clinicopathologic data obtained from our center, we demonstrate that high CA125 serum levels and expression levels of MUC16 are predictive of poor prognosis. MUC16 is also validated as a downstream target of KRAS, and their expression strongly correlated with each other in vitro and in vivo Mechanistically, the KRAS/ERK axis induced upregulation of MUC16 and shedding of CA125 via its effector c-Myc in SW1990 and PANC-1 pancreatic cancer cells. Notably, proto-oncogene c-Myc could bind to the promoter of MUC16 and transcriptionally activate its expression. Taken together, these data establish CA125 as a prognostic marker for pancreatic cancer, and mechanistic studies uncovered the KRAS/c-Myc axis as a driving factor for upregulation of MUC16.
  
  
  
  The current study uncovers the contribution of oncogenic KRAS to serum marker CA125 production through a mechanism that involves the ERK/c-Myc axis. Mol Cancer Res; 15(2); 201-12. ©2016 AACR.
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Shunrong
authors.initials: S
authors.lastname: Ji
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Si
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Dingkong
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Qiangsheng
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Quanxing
authors.initials: Q
authors.lastname: Ni
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. yuxianjun@fudanpci.org xujin@fudanpci.org.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. yuxianjun@fudanpci.org xujin@fudanpci.org.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Pancreatic Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D018394:CA-125 Antigen / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D011519:Proto-Oncogenes; D014162:Transfection
chemical_list: D018394:CA-125 Antigen; C117307:KRAS protein, human; C000715470:MAS1 protein, human; C451759:MUC16 protein, human; C534798:MUC16 protein, mouse; D008565:Membrane Proteins; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras)