TY - JOUR
T1 - The role of HMGB1-RAGE axis in migration and invasion of hepatocellular carcinoma cell lines
AU - Chen, Ruo Chan
AU - Yi, Pan Pan
AU - Zhou, Rong Rong
AU - Xiao, Mei Fang
AU - Huang, Ze Bing
AU - Tang, Dao Lin
AU - Huang, Yan
AU - Fan, Xue Gong
N1 - Funding Information:
Acknowledgments This work was financially supported by the National Natural Science Foundation of China (No. 30972621), the National Natural Science Youth Foundation of China (No. 81101829), and Scientific Foundation of Provincial Department of Public Health (No. 132012008). We thank the Liver Cancer Institute of Fudan University (Shanghai, China) for kindly presenting two cell lines.
PY - 2014/5
Y1 - 2014/5
N2 - High mobility group protein box1 (HMGB1) and its receptor - receptor for advanced glycation end products (RAGE) are pivotal factors in the development and progression of many types of tumor, but the role of HMGB1-RAGE axis in hepatocellular carcinoma (HCC) especially its effects on metastasis and recurrence remains obscure. Here, we report the role of HMGB1-RAGE axis in the biological behaviors of HCC cell lines and the underlying molecular mechanism. We show that the expressions of HMGB1, RAGE, and extracellular HMGB1 increase consistently according to cell metastasis potentials, while the concentration of soluble form of RAGE (sRAGE) is inversely related to metastasis potential of HCC cells. Furthermore, our data show that rhHMGB1 promotes cellular proliferation, migration, and invasion, and increases the level of nuclear factor kappa B (NF-κB), while administrations of HMGB1-siRNA, RAGE-siRNA, anti-HMGB1 neutralizing antibody, anti-RAGE neutralizing antibody, and sRAGE inhibit cellular proliferation, migration, and invasion. Moreover, we also demonstrate that the expression of NF-kB is inhibited by knockdown of HMGB1 or RAGE. Collectively, these data demonstrate that HMGB1 activates RAGE signaling pathways and induces NF-kB activation to promote cellular proliferation, invasion, and metastasis, in HCC cell lines. Taken together, HMGB1-RAGE axis may become a potential target in HCC therapy.
AB - High mobility group protein box1 (HMGB1) and its receptor - receptor for advanced glycation end products (RAGE) are pivotal factors in the development and progression of many types of tumor, but the role of HMGB1-RAGE axis in hepatocellular carcinoma (HCC) especially its effects on metastasis and recurrence remains obscure. Here, we report the role of HMGB1-RAGE axis in the biological behaviors of HCC cell lines and the underlying molecular mechanism. We show that the expressions of HMGB1, RAGE, and extracellular HMGB1 increase consistently according to cell metastasis potentials, while the concentration of soluble form of RAGE (sRAGE) is inversely related to metastasis potential of HCC cells. Furthermore, our data show that rhHMGB1 promotes cellular proliferation, migration, and invasion, and increases the level of nuclear factor kappa B (NF-κB), while administrations of HMGB1-siRNA, RAGE-siRNA, anti-HMGB1 neutralizing antibody, anti-RAGE neutralizing antibody, and sRAGE inhibit cellular proliferation, migration, and invasion. Moreover, we also demonstrate that the expression of NF-kB is inhibited by knockdown of HMGB1 or RAGE. Collectively, these data demonstrate that HMGB1 activates RAGE signaling pathways and induces NF-kB activation to promote cellular proliferation, invasion, and metastasis, in HCC cell lines. Taken together, HMGB1-RAGE axis may become a potential target in HCC therapy.
KW - HMGB1
KW - Hepatocellular carcinoma
KW - Invasion
KW - Migration
KW - RAGE
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U2 - 10.1007/s11010-014-1978-6
DO - 10.1007/s11010-014-1978-6
M3 - Article
C2 - 24510323
AN - SCOPUS:84898910879
SN - 0300-8177
VL - 390
SP - 271
EP - 280
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -