title: The ubiquitin ligase RNF43 downregulation increases membrane expression of frizzled receptor in pancreatic ductal adenocarcinoma.
abstract: RNF43 is a novel tumor suppressor protein and known to be expressed in a multitude of tissue and dysregulated in cancers of these organs including ovarian and colorectal tissues. RNF43 expression has been shown to be expressed in mutated forms in several pancreatic cell lines. RNF43, by virtue of being an ubiquitin ligase, has the potential to ubiquitinylate membrane receptors like frizzled that subserves sensing Wnt soluble signals at the cell membrane. Thus, normally, RNF43 downregulates Wnt signaling by removing frizzled receptor from the membrane. In the present study, the expression of the tumor suppressor RNF43 was examined in human patient samples of pancreatic ductal adenocarcinoma (PDAC). Reduced levels of expression of RNF43 in PDAC were demonstrated by Western blotting. We incorporated membrane biotinylation assay to examine the expression of frizzled6 receptor in the membrane and demonstrated that it is significantly increased in PDAC tissues. This may be responsible for enhanced Wnt/beta-catenin signaling and provides the first level of evidence of a possible role of this well-known pathway in pancreatic exocrine carcinogenesis. We have utilized appropriate controls to ensure the true positivity of the findings of the present study. The contribution of Wnt/beta-catenin/RNF43 pathway in pancreatic carcinogenesis may provide for utilization of pharmacologic resources for precision-based approaches to treat pancreatic ductal adenocarcinoma.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hostpial of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Dadong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hostpial of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Jingwang
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hostpial of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hostpial of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hostpial of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hostpial of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Ziman
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hostpial of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Chunqing
authors.initials: C
authors.lastname: Dou
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hostpial of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xin
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hostpial of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Xianglong
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hostpial of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zeng
authors.affiliation: Department of Emergency Surgery, Qianfoshang Hospital Affiliated to Shandong University, No 16766, Jingshi Road, Lixia Distict, Jinan, 250014, China. zhaogang198@126.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery, Chinese PLA General Hospital, No.28, Fuxing Road, Haidian District, Beijing, 100853, China. zwliu301@163.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
mesh_terms: D065311:Adenocarcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; D051157:Frizzled Receptors; D015513:Oncogene Proteins; C496945:RNF43 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Pancreas; Tumor progression; Tumor suppressor; Wnt signaling