LukS-PV induces differentiation by activating the ERK signaling pathway and c-JUN/c-FOS in human acute myeloid leukemia cells

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• 作者：Chunyang Dai^a ; ¹ ; Chengfang Zhang^a ; ¹ ; Xiaoxi Sun^a ; Qing Pan^b ; Jing Peng^a ; Jilong Shen^c ; Xiaoling Ma^a ; ^{xiaolingma@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Acute myeloid leukemia ; Panton&ndash ; Valentine leukocidin ; Differentiation ; Bacterization ; Extracellular signal-regulated kinase pathway
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：76
• 期：Complete
• 页码：107-114
• 全文大小：2387 K

文摘

LukS-PV, a component of Panton–Valentine leukocidin, is a pore-forming cytotoxin secreted by Staphylococcus aureus. Here we examined the potential effect of LukS-PV in differentiation of human leukemia cells and the underlying mechanism. We found that LukS-PV could induce differentiation of human acute myeloid leukemia (AML) cells, including AML cell lines and primary AML blasts, as determined by morphological changes, phagocytosis assay and expression of CD14 and CD11b surface antigens. In addition, LukS-PV activated the extracellular signal-regulated kinase (ERK) pathway and significantly upregulated the phosphorylation of c-JUN and c-FOS transcriptional factors in the process of differentiation. Inhibiting ERK pathway activation with U0126 (a MEK1/2 inhibitor) markedly blocked LukS-PV-induced differentiation and decreased the phosphorylation of c-JUN and c-FOS. These findings demonstrate an essential role for the ERK pathway together with c-JUN and c-FOS in the differentiation activity of LukS-PV. Taken together, our data suggest that LukS-PV could be a potential candidate as a differentiation-inducing agent for the therapeutic treatment of AML.