title: Extracellular HSPA1A promotes the growth of hepatocarcinoma by augmenting tumor cell proliferation and apoptosis-resistance.
abstract: Intracellular HSP70 has been implicated as a cytoprotective protein, whereas the effect of extracellular HSP70 on tumor cells has not been fully understood to date. Here we report that extracellular HSPA1A, a stress-inducible member of HSP70 family, could promote tumor growth. HSPA1A promoted the proliferation of H22 hepatocarcinoma cells through TLR2 and TLR4 signaling. The effect of HSPA1A was abolished by inhibiting NF-κB. HSPA1A also augmented the apoptosis-resistance of H22 cells by activating NF-κB, thus to promote the proliferation of H22 cells in presence of mitomycin C. Furthermore, the promoting effect of HSPA1A on tumor cell proliferation was existent after the removal of HSPA1A, which might involve HSPA1A-promoted upregulation of TLR4 expression in tumor cells and release of HMGB1 from tumor cells. These findings suggest that extracellular HSPA1A functions as endogenous ligand for TLR2 and TLR4 to facilitate tumor growth.
authors: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, People's Republic of China.
authors: Feng-Hua
authors: FH
authors: Wu
authors: Ye
authors: Y
authors: Yuan
authors: Dong
authors: D
authors: Li
authors: Sheng-Jun
authors: SJ
authors: Liao
authors: Bin
authors: B
authors: Yan
authors: Jing-Jing
authors: JJ
authors: Wei
authors: Yuan-Hong
authors: YH
authors: Zhou
authors: Jian-Hua
authors: JH
authors: Zhu
authors: Gui-Mei
authors: GM
authors: Zhang
authors: Zuo-Hua
authors: ZH
authors: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D018840:HSP70 Heat-Shock Proteins; C490786:HSPA1A protein, human; D016328:NF-kappa B; D011994:Recombinant Proteins; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4