title: Stiehopus japonieus acidic mucopolysaccharide inhibits the proliferation of pancreatic cancer SW1990 cells through Hippo-YAP pathway.
abstract: Previous studies have indicated that stiehopus japonieus acidic mucopolysaccharide (SJAMP) could inhibit the proliferation of pancreatic cancer cell SW1990. However, the mechanism remains unclear. In our study, YAP expression was identified by immunohistochemistry and quantitative Real-time PCR from 45 pairs of human pancreatic ductal adenocarcinoma (PDAC) tissues and their adjacent non-tumor samples. We found that the YAP expression was associated with the histological differentiation degree, and negatively correlated with pancreatic cancer patients' survival. More YAP localization in nuclear and enhanced expression of YAP mRNA in pancreatic cancer tissue was found in comparison with in the normal tissue. These results identify YAP acts as an amazing regulator in the pathogenesis of pancreatic cancer. After affected by SJAMP, YAP and TEAD1 were down regulated, while MST1 and pYAP were upregulated gradually with the prolong of effect time. SJAMP also improved YAP phosphorylation, nuclear-to-cytoplasmic translocation and inactivation. After successfully knocked-down by YAP siRNA, the inhibition of proliferation of SJAMP to cancer cells was attenuated. Interestingly, we indicated a down-regulation of that TEAD with SJAMP 4 mg/ml, 8 mg/ml for 24 h and with 8 mg/ml SJAMP for 24 h, 48 h even after YAP silencing. That might mean that the SJAMP has other targets, not only YAP, to downregulate TEAD. We proposed a hypothesis that Hippo-YAP pathway involved in carcinogenesis of pancreatic cancer and in the inhibition effect of SJAMP to the proliferation of pancreatic cancer cell, although maybe not the sole signaling pathway.
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Shanxian Central Hospital, Heze 274000, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Niu
authors.affiliation: Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Che
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Man
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Zibin
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000143:Acids / Q000737:chemistry; D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006025:Glycosaminoglycans / Q000737:chemistry / Q000494:pharmacology*; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053208:Kaplan-Meier Estimate; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D047528:Stichopus / Q000737:chemistry*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099317:Hippo Kinases
chemical_list: D000143:Acids; D018797:Cell Cycle Proteins; D006025:Glycosaminoglycans; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; D014157:Transcription Factors; C456659:YY1AP1 protein, human; C095566:STK4 protein, human; D000099317:Hippo Kinases; C097835:STK3 protein, human
keywords: Hippo-YAP pathway; PDAC; SJAMP; cell proliferation