title: Leptin promotes proliferation and metastasis of human gallbladder cancer through OB-Rb leptin receptor.
abstract: Emerging evidence has shown that leptin, an adipocyte-derived cytokine that is closely associated with obesity, play a significant role in carcinogenesis and tumorigenesis. However, its impact on gallbladder cancer (GBC) remains unclear. In this study, we firstly found that leptin and its functional receptor OB-Rb were significantly co-expressed in human GBC tissues and cell lines, the content of which were higher than those in normal human gallbladder tissues. Treatment with leptin promoted the proliferation, migration and invasion of GBC cells, which were attenuated by OB-Rb shRNA. Blocking in the G2/M period of cell cycle, increasing of MMP3 and MMP9, increasing of VEGF-C/D, activation of SOCS3/JAK2/p-STAT3 pathway was demonstrated after treatment with leptin. All of these positive responses were attenuated by OB-Rb receptor shRNA. Taken together, our findings suggest that leptin promoted the proliferation, migration and invasion of GBC cells by increasing OB-Rb expression through the SOCS3/JAK2/p-STAT3 signal pathway. Targeting the leptin/OB-Rb axis could be an attractive therapeutic strategy for treatment of GBC.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zou
authors.affiliation: Experiment Teaching Center, Basic Medical School, Kunming Medical University, Kunming, Yunnan 650500, P.R. China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Songquan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Jiayun
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Lianmin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Songling
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
mesh_terms: D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D005706:Gallbladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D020738:Leptin / Q000008:administration & dosage / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering; D054411:Receptors, Leptin / Q000096:biosynthesis / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics
chemical_list: C515448:LEPR protein, human; D020738:Leptin; D034741:RNA, Small Interfering; D054411:Receptors, Leptin; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; C507924:JAK2 protein, human; D053614:Janus Kinase 2