Mesenchymal stem cells promote metastasis through activation of an ABL-MMP9 signaling axis in lung cancer cells.
Mesenchymal stem cells promote metastasis through activation of an ABL-MMP9 signaling axis in lung cancer cells.
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DOI：
10.1371/journal.pone.0241423
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Pendergast AM
中科院分区：
文献类型：
--
作者：
Gu JJ;Hoj J;Rouse C;Pendergast AM
间充质干细胞（MSC）被实体瘤募集和激活，并在肿瘤进展和转移中发挥作用。在这里，我们表明，骨髓间充质干细胞促进转移的一组非小细胞肺癌（NSCLC）细胞。MSC引起肺癌细胞中的转录改变，导致上皮-间充质转化（EMT）中涉及的因子和分泌的蛋白质（包括基质金属蛋白酶-9（MMP 9））的表达增加。间充质干细胞增强一组肺腺癌细胞中酶活性MMP 9的分泌。MMP 9高表达与肺腺癌患者的低生存率相关值得注意的是，我们发现ABL酪氨酸激酶在MSC引发的肺癌细胞中被激活，并且功能性ABL激酶是MSC诱导的MMP 9表达、分泌和蛋白水解活性所需的。重要的是，ABL激酶是MSC诱导的NSCLC转移所必需的。这些数据揭示了通过破坏在MSC引发的肺癌细胞中激活的ABL激酶-MMP 9信号传导轴来抑制MSC诱导的肺腺癌细胞转移活性的可行靶标。
Mesenchymal stem cells (MSCs) are recruited and activated by solid tumors and play a role in tumor progression and metastasis. Here we show that MSCs promote metastasis in a panel of non-small cell lung cancer (NSCLC) cells. MSCs elicit transcriptional alterations in lung cancer cells leading to increased expression of factors implicated in the epithelial-to-mesenchymal transition (EMT) and secreted proteins including matrix metalloproteinase-9 (MMP9). MSCs enhance secretion of enzymatically active MMP9 in a panel of lung adenocarcinoma cells. High expression of MMP9 is linked to low survival rates in lung adenocarcinoma patients. Notably, we found that ABL tyrosine kinases are activated in MSC-primed lung cancer cells and functional ABL kinases are required for MSC-induced MMP9 expression, secretion and proteolytic activity. Importantly, ABL kinases are required for MSC-induced NSCLC metastasis. These data reveal an actionable target for inhibiting MSC-induced metastatic activity of lung adenocarcinoma cells through disruption of an ABL kinase-MMP9 signaling axis activated in MSC-primed lung cancer cells.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
15.9
作者：
Chaturvedi, Pallavi;Gilkes, Daniele M.;Semenza, Gregg L.
通讯作者：
Semenza, Gregg L.
DOI：
10.1186/s12964-016-0143-0
发表时间：
2016-09-08
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Melzer C;Yang Y;Hass R
通讯作者：
Hass R
影响因子：
--
作者：
Mehner C;Hockla A;Miller E;Ran S;Radisky DC;Radisky ES
通讯作者：
Radisky ES
影响因子：
11.1
作者：
Fregni, Giulia;Quinodoz, Mathieu;Stamenkovic, Ivan
通讯作者：
Stamenkovic, Ivan