PMID- 23836405 OWN - NLM STAT- MEDLINE DCOM- 20140612 LR - 20131024 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 30 IP - 3 DP - 2013 Sep TI - Invasion potential of H22 hepatocarcinoma cells is increased by HMGB1-induced tumor NF-kappaB signaling via initiation of HSP70. PG - 1249-56 LID - 10.3892/or.2013.2595 [doi] AB - The functional relationship and cross-regulation between damage-associated molecular patterns and NF‑kappaB in the tumor microenvironment remains unclear. In the present study, high-mobility group protein B1 (HMGB1) was secreted in response to feed second phase of NF‑kappaB activation from heat shock protein (HSP) 70 that may result in a higher invasion potential of hepatocarcinoma cells. HSP70 promoted the proliferation of H22 hepatocarcinoma cells through Toll-like receptor (TLR) 2 and TLR4 signaling and induced the early phosphorylation of NF-kappaB, which reached maximum levels within 30 min. However, HSP70 promoted the upregulation of Beclin-1 expression via Jun N-terminal kinase (JNK) activation in tumor cells and the release of HMGB1 from tumor cells. Inhibition of Beclin-1/c-JNK production prevented the second, but not the first, phase of NF-kappaB phosphorylation, implicating Beclin-1/c-JNK in the second phase of phosphorylation. HSP70 induced Beclin-1-derived HMGB1 production at 4 h, which occurred before the rise in the second phosphorylation that occurred at 6 h. Exogenous HMGB1 also induced the rapid phosphorylation of NF-kappaB and upregulated the expression of MMP-9, inhibited the rapid phosphorylation of NF-kappaB and reduced MMP-9 by receptor for advanced glycation end products (RAGE) inhibitor that prevented HMGB1-induced cell invasion in vitro, which demonstrated that the biological significance of HMGB1/RAGE is key to the second, but not the first, phase of NF-kappaB phosphorylation in tumor cells. HSP70 triggered a positive feedback loop of NF-kappaB activation in H22 cells. The second phase of NF-kappaB phosphorylation mediated by HSP70 is implicated in the increase of tumor cell malignant invasion. FAU - Gong, Wei AU - Gong W AD - Department of Oncology, XiangYang Central Hospital, Hubei University of Arts and Science, XiangYang, Hubei 441021, P.R. China. FAU - Wang, Zhi-Yong AU - Wang ZY FAU - Chen, Guo-Xi AU - Chen GX FAU - Liu, Yu-Qiao AU - Liu YQ FAU - Gu, Xiao-Yan AU - Gu XY FAU - Liu, Wen-Wei AU - Liu WW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130705 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, human) RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - EC 3.4.24.35 (MMP9 protein, human) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Apoptosis MH - Blotting, Western MH - Carcinoma, Hepatocellular/genetics/metabolism/*pathology MH - Cell Proliferation MH - Flow Cytometry MH - HMGB1 Protein/antagonists & inhibitors/genetics/*metabolism MH - HSP70 Heat-Shock Proteins/genetics/*metabolism MH - Humans MH - Liver Neoplasms/genetics/metabolism/*pathology MH - Matrix Metalloproteinase 9/genetics/metabolism MH - Mice MH - Mice, Inbred BALB C MH - NF-kappa B/genetics/*metabolism MH - Neoplasm Invasiveness MH - Phosphorylation MH - RNA, Messenger/genetics MH - RNA, Small Interfering/genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Cells, Cultured MH - Xenograft Model Antitumor Assays EDAT- 2013/07/10 06:00 MHDA- 2014/06/13 06:00 CRDT- 2013/07/10 06:00 PHST- 2013/05/01 00:00 [received] PHST- 2013/06/03 00:00 [accepted] PHST- 2013/07/10 06:00 [entrez] PHST- 2013/07/10 06:00 [pubmed] PHST- 2014/06/13 06:00 [medline] AID - 10.3892/or.2013.2595 [doi] PST - ppublish SO - Oncol Rep. 2013 Sep;30(3):1249-56. doi: 10.3892/or.2013.2595. Epub 2013 Jul 5.