S100A14 stimulates cell proliferation and induces cell apoptosis at different concentrations via receptor for advanced glycation end products (RAGE).
S100A14 stimulates cell proliferation and induces cell apoptosis at different concentrations via receptor for advanced glycation end products (RAGE).
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S100A14 在不同浓度下通过高级糖基化终产物 (RAGE) 受体刺激细胞增殖并诱导细胞凋亡
DOI：
10.1371/journal.pone.0019375
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发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Jin Q;Chen H;Luo A;Ding F;Liu Z
S100A14是S100蛋白家族中一种含EF-Hand的钙结合蛋白，对不同类型的细胞具有生物学效应。然而，S100A14在细胞外的确切作用还不是很清楚。在此，我们研究了S100A14对食管鳞癌(ESCC)细胞系的作用。结果表明，低剂量的胞外S100A14通过激活ERK1/2MAPK和NF-κB信号通路，促进KYSE180细胞增殖和存活。免疫沉淀分析表明，S100A14与KYSE180细胞的晚期糖基化终产物受体(RAGE)结合。不同的方法抑制RAGE信号，包括RAGE的siRNA、显性负性RAGE结构的过表达或RAGE拮抗肽(AmphP)的过表达，均可显著阻断S100A14的作用，提示S100A14通过RAGE结扎发挥作用。此外，S100A14(E39A、E45A)的N-EF手部突变显著降低了10µg/mlS100A14诱导的细胞增殖和ERK1/2的激活。然而，高剂量(80µg/ml)的S100A14通过激活caspase-3、caspase-9和聚(ADP-核糖)聚合酶而通过线粒体途径诱导细胞凋亡。大剂量S100A14诱导细胞凋亡部分以RAGE依赖的方式进行。这是第一个证明S100A14与RAGE结合并刺激RAGE依赖的信号级联反应，在不同剂量促进细胞增殖或触发细胞凋亡的研究。
S100A14 is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effects on different types of cells. However, exact extracellular roles of S100A14 have not been clarified yet. Here we investigated the effects of S100A14 on esophageal squamous cell carcinoma (ESCC) cell lines. Results demonstrated that low doses of extracellular S100A14 stimulate cell proliferation and promote survival in KYSE180 cells through activating ERK1/2 MAPK and NF-κB signaling pathways. Immunoprecipitation assay showed that S100A14 binds to receptor for advanced glycation end products (RAGE) in KYSE180 cells. Inhibition of RAGE signaling by different approaches including siRNA for RAGE, overexpression of a dominant-negative RAGE construct or a RAGE antagonist peptide (AmphP) significantly blocked S100A14-induced effects, suggesting that S100A14 acts via RAGE ligation. Furthermore, mutation of the N-EF hand of S100A14 (E39A, E45A) virtually reduced 10 µg/ml S100A14-induced cell proliferation and ERK1/2 activation. However, high dose (80 µg/ml) of S100A14 causes apoptosis via the mitochondrial pathway with activation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase. High dose S100A14 induces cell apoptosis is partially in a RAGE-dependent manner. This is the first study to demonstrate that S100A14 binds to RAGE and stimulates RAGE-dependent signaling cascades, promoting cell proliferation or triggering cell apoptosis at different doses.
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DOI：
10.1016/j.bbrc.2004.02.135
发表时间：
2004-04-09
影响因子：
3.1
作者：
Hsieh, HL;Schäfer, BW;Heizmann, CW
通讯作者：
Heizmann, CW
影响因子：
3.9
作者：
Fuentes, Maren K.;Nigavekar, Shraddha S.;Huang, Emina H.
通讯作者：
Huang, Emina H.
影响因子：
4.8
作者：
Leclerc, Estelle;Fritz, Gunter;Galichet, Arnaud
通讯作者：
Galichet, Arnaud
影响因子：
4.8
作者：
Adam, PJ;Boyd, R;Terrett, JA
通讯作者：
Terrett, JA
影响因子：
4.8
作者：
Huttunen, HJ;Fages, C;Rauvala, H
通讯作者：
Rauvala, H