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Title: HMGB1 induces human non-small cell lung cancer cell motility by activating integrin αvβ3/FAK through TLR4/NF-κB signaling pathway

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [3]; ; ;  [1];  [4]
  1. Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei (China)
  2. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei (China)
  3. Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei (China)
  4. Department of Endocrinology, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei (China)

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. - Highlights: • HMGB1 induces A549 and H838 cells migration and invasion. • HMGB1 increases integrin αvβ3 expression through TLR4/NF-κB pathway. • HMGB1 activates FAK and increases paxillin and talin expression through activating αvβ3.

OSTI ID:
22696705
Journal Information:
Biochemical and Biophysical Research Communications, Vol. 480, Issue 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
Country of Publication:
United States
Language:
English