title: DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer.
abstract: DUSP1/MKP1 is a dual-specific phosphatase that regulates MAPK activity and is known to play a key role in tumor biology. Its function in gallbladder cancer (GBC) remains largely unknown, however. By exploring its activities in two GBC cell lines (SGC996 and GBC-SD), DUSP1 was found to inhibit GBC cell proliferation, migration and invasion. Moreover, DUSP1 inhibited GBC growth and metastasis in nude mice subcutaneously xenografted with SGC996 cells. The tumor suppression appeared to be mediated via the DUSP1-pERK/MAPK-MMP2 signal pathway. Angiogenesis was associated with the tumor metastasis in the mouse model and was impaired by DUSP1, which suppressed VEGF expression. These results suggest that DUSP1 suppresses GBC growth and metastasis by targeting the DUSP1-pERK-MMP2/VEGF axis. Identification of the DUSP1-pERK-MMP2/VEGF signals may provide new biomarkers and/or therapeutic targets to better suppress GBC metastasis in the future.
authors.affiliation: Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Senjun
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.lastname: Xiaoliang
authors.affiliation: Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Tunan
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
authors.forename: Xiujun
authors.initials: X
authors.lastname: Cai
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005706:Gallbladder Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D048049:Extracellular Signal-Regulated MAP Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D020778:Matrix Metalloproteinase 2
keywords: DUSP1; MMP2; angiogenesis; gallbladder cancer; metastasis