S100A8 contributes to drug resistance by promoting autophagy in leukemia cells.
S100A8 contributes to drug resistance by promoting autophagy in leukemia cells.
复制标题
S100A8 通过促进白血病细胞自噬导致耐药性
DOI：
10.1371/journal.pone.0097242
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cao L
中科院分区：
文献类型：
--
作者：
Yang M;Zeng P;Kang R;Yu Y;Yang L;Tang D;Cao L
自噬在肿瘤发生过程中是一把双刃剑，在癌细胞对化疗的抵抗中起着重要作用。S100A8是S100钙结合蛋白家族的一员，在白血病细胞的耐药过程中发挥重要作用，但其机制尚不清楚。在这里，我们报道S100A8通过促进自噬来促进白血病的耐药。耐药白血病细胞株中S100A8水平明显高于非耐药白血病细胞株。阿霉素和长春新碱增加了人白血病细胞中的S100A8，并伴有自噬的上调。RNA干扰介导的S100A8的下调恢复了白血病细胞的化疗敏感性，而S100A8的过表达增强了白血病细胞的耐药性，增加了自噬。S100A8物理上与自噬调节因子BECN1相互作用，是BECN1- pi3kc3复合物形成所必需的。此外，S100A8与BECN1之间的相互作用依赖于自噬复合体ULK1-mAtg13。此外，我们发现外源性S100A8诱导自噬，RAGE参与了外源性S100A8调控的自噬。我们的数据表明，S100A8通过调节自噬参与白血病细胞化疗耐药的发展，提示S100A8可能是改善白血病治疗的新靶点。
Autophagy is a double-edged sword in tumorigenesis and plays an important role in the resistance of cancer cells to chemotherapy. S100A8 is a member of the S100 calcium-binding protein family and plays an important role in the drug resistance of leukemia cells, with the mechanisms largely unknown. Here we report that S100A8 contributes to drug resistance in leukemia by promoting autophagy. S100A8 level was elevated in drug resistance leukemia cell lines relative to the nondrug resistant cell lines. Adriamycin and vincristine increased S100A8 in human leukemia cells, accompanied with upregulation of autophagy. RNA interference-mediated knockdown of S100A8 restored the chemosensitivity of leukemia cells, while overexpression of S100A8 enhanced drug resistance and increased autophagy. S100A8 physically interacted with the autophagy regulator BECN1 and was required for the formation of the BECN1-PI3KC3 complex. In addition, interaction between S100A8 and BECN1 relied upon the autophagic complex ULK1-mAtg13. Furthermore, we discovered that exogenous S100A8 induced autophagy, and RAGE was involved in exogenous S100A8-regulated autophagy. Our data demonstrated that S100A8 is involved in the development of chemoresistance in leukemia cells by regulating autophagy, and suggest that S100A8 may be a novel target for improving leukemia therapy.
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
16
作者：
Kroemer G;Mariño G;Levine B
通讯作者：
Levine B
影响因子：
30.8
作者：
Ravikumar, B;Vacher, C;Rubinsztein, DC
通讯作者：
Rubinsztein, DC
DOI：
10.1016/j.bbamcr.2007.10.015
发表时间：
2008-02-01
影响因子：
5.1
作者：
Ghavami, Saeld;Kerkhoff, Claus;Los, Marek
通讯作者：
Los, Marek
影响因子：
7.7
作者：
Kihara, A;Kabeya, Y;Yoshimori, T
通讯作者：
Yoshimori, T