The IGF2/IGF1R/Nanog Signaling Pathway Regulates the Proliferation of Acute Myeloid Leukemia Stem Cells.
The IGF2/IGF1R/Nanog Signaling Pathway Regulates the Proliferation of Acute Myeloid Leukemia Stem Cells.
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IGF2/IGF1R/Nanog信号通路调节急性髓系白血病干细胞的增殖
DOI：
10.3389/fphar.2018.00687
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发表时间：
2018
影响因子：
5.6
通讯作者：
Wang YF
中科院分区：
文献类型：
--
作者：
Xu DD;Wang Y;Zhou PJ;Qin SR;Zhang R;Zhang Y;Xue X;Wang J;Wang X;Chen HC;Wang X;Pan YW;Zhang L;Yan HZ;Liu QY;Liu Z;Chen SH;Chen HY;Wang YF
急性髓系白血病是一种侵袭性疾病，其特征是克隆增殖并分化为功能失调的髓系前体细胞的未成熟造血细胞。越来越多的证据表明，CD34+CD38-白血病干细胞（LSC）与白血病的耐药、转移和复发有关。在这项研究中，我们发现 Nanog（干细胞中的一种转录因子）在急性髓系白血病患者的 CD34+ 群体和白血病细胞系的 LSC 中显着过度表达。我们的数据表明，Nanog 的敲低抑制了增殖并诱导细胞周期停滞和细胞凋亡。此外，Nanog 沉默抑制了小鼠 LSC 的白血病发生。此外，我们发现Nanog的这些功能受到胰岛素样生长因子受体（IGF1R）信号通路的调节。 Nanog 过表达可挽救经鬼臼苦素 (PPP)（一种 IGF1R 抑制剂）处理的 LSC 的集落形成能力。相比之下，Nanog 的敲低消除了 IGF2 对这些 LSC 集落形成能力的影响。这些发现表明 IGF2/IGF1R/Nanog 信号通路在 LSC 增殖中发挥着关键作用。
Acute myeloid leukemia is an aggressive disease characterized by clonal proliferation and differentiation into immature hematopoietic cells of dysfunctional myeloid precursors. Accumulating evidence shows that CD34+CD38- leukemia stem cells (LSCs) are responsible for drug resistance, metastasis, and relapse of leukemia. In this study, we found that Nanog, a transcription factor in stem cells, is significantly overexpressed in CD34+ populations from patients with acute myeloid leukemia and in LSCs from leukemia cell lines. Our data demonstrate that the knockdown of Nanog inhibited proliferation and induced cell cycle arrest and cell apoptosis. Moreover, Nanog silencing suppressed the leukemogenesis of LSCs in mice. In addition, we found that these functions of Nanog were regulated by the insulin-like growth factor receptor (IGF1R) signaling pathway. Nanog overexpression rescued the colony formation ability of LSCs treated with picropodophyllin (PPP), an IGF1R inhibitor. By contrast, knockdown of Nanog abolished the effects of IGF2 on the colony formation ability of these LSCs. These findings suggest that the IGF2/IGF1R/Nanog signaling pathway plays a critical role in LSC proliferation.
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影响因子：
8
作者：
Jeter, C. R.;Liu, B.;Liu, X.;Chen, X.;Liu, C.;Calhoun-Davis, T.;Repass, J.;Zaehres, H.;Shen, J. J.;Tang, D. G.
通讯作者：
Tang, D. G.
影响因子：
14.9
作者：
Eberle I;Pless B;Braun M;Dingermann T;Marschalek R
通讯作者：
Marschalek R
癌症相关成纤维细胞通过旁分泌信号调节肺癌干细胞的可塑性
影响因子：
16.6
作者：
Chen, Wan-Jiun;Ho, Chao-Chi;Yang, Pan-Chyr
通讯作者：
Yang, Pan-Chyr
影响因子：
11.5
作者：
Chiou, Shih-Hwa;Yu, Cheng-Chia;Lo, Jeng-Fan
通讯作者：
Lo, Jeng-Fan
影响因子：
5.7
作者：
Carboni, Joan M.;Wittman, Mark;Gottardis, Marco M.
通讯作者：
Gottardis, Marco M.