NIDO, AMOP and vWD domains of MUC4 play synergic role in MUC4 mediated signaling
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Yi Zhu1,2,3,*, Jing-Jing Zhang1,2,3,*, Yun-Peng Peng1,2,3,*, Xian Liu1,2,3, Kun-Ling Xie3,4, Jie Tang3,5, Kui-Rong Jiang1,2,3, Wen-Tao Gao1,2,3, Lei Tian1,2,3, Kai Zhang1,2,3, Ze-Kuan Xu3, Yi Miao1,2,3
1Pancreas Institute of Nanjing Medical University, Nanjing, People’s Republic of China
2Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
3Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
4Department of General Surgery, The People’s Hospital of Bozhou, Bozhou, Anhui, People’s Republic of China
5Department of Pediatric Surgery, Nanjing Children’s Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China
*These authors have contributed equally to this work
Zekuan Xu, email: email@example.com
Yi Miao, email: firstname.lastname@example.org
Keywords: NIDO, AMOP, vWD, synergy, MUC4/Y
Received: June 20, 2016 Accepted: December 13, 2016 Published: January 02, 2017
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.
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