title: Ninjurin1 suppresses metastatic property of lung cancer cells through inhibition of interleukin 6 signaling pathway.
abstract: Nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a cell surface molecule that can mediate homophilic adhesion and promote neurite outgrowth from cultured dorsal root ganglion (DRG) neurons. Interestingly, Ninj1 overexpressed in human cancer; however, its role in metastasis is not clear. This study showed that inhibition of Ninj1 promotes lung cancer metastasis through interleukin 6 (IL-6)/STAT3 signaling. Ninj1 levels were relatively low in highly motile lung cancer cells. While inhibition of Ninj1 enhanced cell migration in lung cancer cells, overexpression of Ninj1 significantly suppressed it. We found that inhibition of Ninj1 significantly increased expression and secretion of IL-6 in A549 cells. We also found that inhibition of IL-6 decreased intercellular adhesion molecule 1 (ICAM-1) expression. In addition, inhibition of Ninj1 significantly increased cell motility and invasiveness of lung cancer cells. In an in vivo model, we found that Ninj1 suppression did not affect tumor growth but induced significant increase in incidence of lung metastasis, and sizes and number of tumor nodules. Taken together, our data clearly demonstrate that Ninj1 suppresses migration, invasion and metastasis of lung cancer via inhibition of the IL-6 signaling pathway in vitro and in vivo.
authors.affiliation: Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Republic of Korea.
authors.forename: Yeong-Su
authors.initials: YS
authors.lastname: Jang
authors.affiliation: Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Republic of Korea.|National Cancer Center, Goyang-Si, Gyeonggi-Do, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Republic of Korea.
authors.forename: Jong Kyu
authors.initials: JK
authors.lastname: Woo
authors.affiliation: Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Republic of Korea.
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Graduate School of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Jong-Ik
authors.initials: JI
authors.lastname: Hwang
authors.affiliation: National Cancer Center, Goyang-Si, Gyeonggi-Do, Republic of Korea.
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Republic of Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Oh
mesh_terms: D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009362:Neoplasm Metastasis; D009414:Nerve Growth Factors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D015850:Interleukin-6; C484438:NINJ1 protein, human; D009414:Nerve Growth Factors; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D018799:Intercellular Adhesion Molecule-1
keywords: intercellular adhesion molecule 1; interleukin 6; lung cancer; metastasis; nerve injury-induced protein 1