title: NIDO, AMOP and vWD domains of MUC4 play synergic role in MUC4 mediated signaling.
abstract: MUC4 mucin is well known as an important potential target to overcome pancreatic cancer. Three unique domains (NIDO, AMOP, and vWD) with unclear roles only present in MUC4 but are not found in other membrane-bound mucins. Our previous studies first reported that its splice variant, MUC4/Y can be a model of MUC4 (MUC4 gene fragment is more than 30KB, too huge to clone and eukaryotic express) in pancreatic cancer. More importantly, based on MUC4/Y with the appropriate length of gene sequence, it is easy to construct the unique domain-lacking models of MUC4/Y (MUC4) for research. The present study focuses on investigation of the respective role of the unique NIDO, AMOP, and vWD domain or their synergistic effect on MUC4(MUC4/Y)-mediated functions and mechanisms by series of in vitro assays, sequence-based transcriptome analysis, validation of qRT-PCR & Western blot, and systematic comparative analysis. Our results demonstrate: 1) NIDO, AMOP, and vWD domain or their synergy play significant roles on MUC4/Y-mediated malignant function of pancreatic cancer, downstream of molecule mechanisms, particularly MUC4/Y-triggered malignancy-related positive feedback loops, respectively. 2) The synergistic roles of three unique domains on MUC4/Y-mediated functions and mechanisms are more prominent than the respective domain because the synergy of three domain plays the more remarkable effects on MUC4/Y-mediated signaling hub. Thus, to improve reversed effects of domain-lacking and break the synergism of domains will contribute to block MUC4/Y(MUC4) triggering various oncogenic signaling pathways.
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China.|Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China.|Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China.|Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Peng
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China.|Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of General Surgery, The People's Hospital of Bozhou, Bozhou, Anhui, People's Republic of China.
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Xie
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China.|Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Kui-Rong
authors.initials: KR
authors.lastname: Jiang
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China.|Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Gao
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China.|Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China.|Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Ze-Kuan
authors.initials: ZK
authors.lastname: Xu
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing, People's Republic of China.|Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.|Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Miao
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D030541:Databases, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055264:Mucin-4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000072417:Protein Domains; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013997:Time Factors; D014162:Transfection
chemical_list: C524658:MUC4 protein, human; D055264:Mucin-4
keywords: AMOP; MUC4/Y; NIDO; synergy; vWD