title: Leukemia inhibitory factor receptor negatively regulates the metastasis of pancreatic cancer cells in vitro and in vivo.
abstract: Pancreatic cancer (PC) is one of the leading causes of cancer-related deaths worldwide. Frequent metastasis and recurrence are the main reasons for the poor prognosis of PC patients. Thus, the discovery of new biomarkers and wider insights into the mechanisms involved in pancreatic tumorigenesis and metastasis is crucial. In the present study, we report that leukemia inhibitory factor receptor (LIFR) suppresses tumorigenesis and metastasis of PC cells both in vitro and in vivo. LIFR expression was significantly lower in PC tissues and was associated with local invasion (P=0.047), lymph node metastasis (P=0.014) and tumor-node-metastasis (TNM) stage (P=0.002). Overexpression of LIFR significantly suppressed PC cell colony formation (P=0.005), migration (P=0.003), invasion (P=0.010) and wound healing ability (P=0.013) in vitro, while opposing results were observed after LIFR was silenced. Furthermore, animal xenograft and metastasis models confirm that the in vivo results were consistent with the outcomes in vitro. Meanwhile, LIFR inhibited the expression of β-catenin, vimentin and slug and induced the expression of E-cadherin, suggesting that the epithelial-mesenchymal transition regulation pathway may underlie the mechanism. These results indicate that LIFR negatively regulates the metastasis of PC cells.
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Baiyong
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Bingrui
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Chenghong
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Qiu
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000235:genetics*; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D014746:Vimentin / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D015820:Cadherins; C507840:LIFR protein, human; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D014746:Vimentin; D051176:beta Catenin