细胞外
生物
细胞生长
下调和上调
细胞凋亡
细胞生物学
癌症研究
生物化学
基因
作者
Fenghua Wu,Ye Yuan,Dong Li,Shengjun Liao,Bin Yan,Jingjing Wei,Yi Zhou,Jianhua Zhu,Guimei Zhang,Zuo-Hua Feng
出处
期刊:Cancer Letters
[Elsevier]
日期:2012-04-01
卷期号:317 (2): 157-164
被引量:42
标识
DOI:10.1016/j.canlet.2011.11.020
摘要
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.
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