title: Activation of the JAK-STAT3 pathway is associated with the growth of colorectal carcinoma cells.
abstract: Excessive activation of inflammatory signaling pathways facilitates colorectal carcinoma (CRC) malignancy. Continuous activation of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway plays a central role in the development and progression of CRC. With the intent to explore whether attenuation of the JAK-STAT3 signaling axis inhibits cancer cell proliferation or induces apoptosis, a sophisticated oncolytic adenoviral vector, AdCN305, carrying the SOCS3 gene was used to treat CRC cells. Our data revealed that i) in CRC cells, STAT3 was continuously activated by phosphorylation, and SOCS3 was at a relative low expression level; and ii) AdCN305-cppSOCS3 inhibited the continuous activation of the JAK/STAT3 pathway, suppressed CRC cell growth and induced apoptosis, in vitro and in vivo. We proved that SOCS3, a negative regulator of the JAK-STAT3 pathway, efficiently inhibited the activation of the pathway and decreased levels of downstream factors which regulate cell proliferation and the cell cycle.
authors.affiliation: School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, P.R. China.
authors.forename: Xubin
authors.initials: X
authors.lastname: Wei
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xupang
authors.initials: X
authors.lastname: Hu
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Huang
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Wenjia
authors.initials: W
authors.lastname: Lou
authors.forename: Jia
authors.initials: J
authors.lastname: Wu
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.forename: Qibin
authors.initials: Q
authors.lastname: Lou
authors.forename: Chen
authors.initials: C
authors.lastname: Qian
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D005260:Female; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D050504:Oncolytic Viruses; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases