title: Non-tumor tissue derived interleukin-17B activates IL-17RB/AKT/β-catenin pathway to enhance the stemness of gastric cancer.
abstract: Inflammation is a critical component involved in tumor progression. Interleukin-17 (IL-17) belongs to a relatively new family of cytokines that has been associated with the progression of cancers. However, the role of IL-17B/IL-17RB (IL-17 receptor B) signaling to stemness of gastric cancer remains unknown. Here, we confirmed that the expression of IL-17RB in gastric cancer tissues was significantly increased, that overexpression was associated with poor prognosis of gastric cancer patients, and that overexpression was positively correlated with some stemness markers. Interestingly, the expression of IL-17B was upregulated in patient serum rather than gastric tumor tissues. Furthermore, exogenous rIL-17B significantly promoted the stemness of gastric cancer cells depending on IL-17RB and induced the expression of IL-17RB. Simultaneously, the expression of phosphorylated AKT, GSK-3β, and β-catenin as well as the nuclear translocation of β-catenin were significantly increased in the MGC-803 cell in a dose-dependent manner, when treated with rIL-17B. The AKT inhibitor, LY294002, and the knockdown of AKT expression reversed the rIL-17B-induced upregulation of β-catenin and some stemness markers. Together, our results indicate that the IL-17B/IL-17RB signal can promote the growth and migration of tumor cells, and upregulate cell stemness through activating the AKT/β-catenin pathway in gastric cancer, suggesting that IL-17RB may be a novel target in human gastric cancer therapy.
authors.affiliation: Department of Immunology, School of medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Qingli
authors.initials: Q
authors.lastname: Bie
authors.affiliation: Department of Anesthesiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Sun
authors.affiliation: Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gong
authors.affiliation: Department of Anesthesiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Chunye
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Immunology, School of medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.|Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Immunology, School of medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Immunology, School of medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Immunology, School of medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Immunology, School of medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.|Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Immunology, School of medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.|Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.|Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China.
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D018450:Disease Progression; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D051176:beta Catenin / Q000235:genetics / Q000276:immunology*
chemical_list: C495270:CTNNB1 protein, human; D002867:Chromones; D020381:Interleukin-17; D009025:Morpholines; D034741:RNA, Small Interfering; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins; D051176:beta Catenin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt