title: HMGB1 induces human non-small cell lung cancer cell motility by activating integrin αvβ3/FAK through TLR4/NF-κB signaling pathway.
abstract: High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein with multi-functions and plays an important role in tumorigenesis and metastasis in various human cancers. In the present study, we found that HMGB1 induced migration of in human non-small cell lung cancer (NSCLC) cells by up-regulating integrin αvβ3 expression. Further investigation evidenced that HMGB1 activated Toll-like receptor 4 (TLR4) and NF-κB, which was responsible for αvβ3 up-regulation. Furthermore, HMGB1-induced integrin αvβ3 expression led to focal adhesion kinase (FAK) phosphorylation and increased paxillin and talin mRNA expression. Knockdown HMGB1 inhibited xenograft tumor metastasis in athymic mice. Taken together, our findings suggested that HMGB1 enhances tumor cell migration ability by activating αvβ3/FAK through TLR4/NF-κB signaling, leading to metastasis of NSCLC.
authors: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China. Electronic address: zhujh621@163.com.
authors: Jianhua
authors: J
authors: Zhu
authors: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors: Jing
authors: J
authors: Luo
authors: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors: Yongchao
authors: Y
authors: Li
authors: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors: Min
authors: M
authors: Jia
authors: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors: Yueqin
authors: Y
authors: Wang
authors: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors: Yan
authors: Y
authors: Huang
authors: Department of Endocrinology, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors: Shuhong
authors: S
authors: Ke
mesh_terms: D000072283:A549 Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000503:physiopathology*; D002465:Cell Movement; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000473:pathology / Q000503:physiopathology*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D039302:Integrin alphaVbeta3; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: FAK; HMGB1; Migration; NSCLC; TLR4; αvβ3