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

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.