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Ghrelin is a gastric acyl-peptide that plays an important role in cell proliferation. In the present study, we explored the role of ghrelin in A549 cell proliferation and the possible molecular mechanisms. We found that ghrelin promotes A549 cell proliferation, knockdown of the growth hormone secretagogue receptor (GHSR) attenuated A549 cell proliferation caused by ghrelin. Ghrelin induced the rapid phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, ERK, mammalian target of rapamycin (mTOR) and P70S6K. PI3K inhibitor (LY 294002), ERK inhibitor (PD98059) and mTOR inhibitor (Rapamycin) inhibited ghrelin-induced A549 cell proliferation. Moreover, GHSR siRNA inhibited phosphorylation of PI3K, Akt, ERK, mTOR and P70S6K induced by ghrelin. Akt and mTOR/P70S6K phosphorylation was inhibited by LY 294002 but not by PD98059. These results indicate that ghrelin promotes A549 cell proliferation via GHSR-dependent PI3K/Akt/mTOR/P70S6K and ERK signaling pathways. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]