Blockade of Notch3 inhibits the stem-like property and is associated with ALDH1A1 and CD44 via autophagy in non-small lung cancer
Blockade of Notch3 inhibits the stem-like property and is associated with ALDH1A1 and CD44 via autophagy in non-small lung cancer
复制标题
阻断 Notch3 可抑制非小细胞肺癌中的干细胞样特性，并通过自噬与 ALDH1A1 和 CD44 相关
DOI：
10.3892/ijo.2016.3464
复制
发表时间：
2016-06-01
影响因子：
5.2
通讯作者：
Yang, Yue
中科院分区：
文献类型：
--
作者：
Ma, Yuanyuan;Li, Mingzhen;Yang, Yue
对标准化疗的获得性耐药导致局部晚期和晚期非小细胞肺癌（NSCLC）患者治疗失败。癌症干细胞（CSC）是癌症中的一个小亚群，被认为对常规化疗具有抗性。Notch通路是实体瘤中CSC的假定治疗靶点的最深入研究之一。在我们的研究中，Notch3的抑制降低了肺癌细胞中干细胞样特性的集落和球体形成。此外，Notch3在化疗耐药患者中表达上调，并与NSCLC患者的不良预后相关。我们的研究结果还显示CSC标志物ALDH1A1和CD44在具有化疗耐药的NSCLC患者中高表达，并且这两个标志物与TCGA数据库中肺癌标本中Notch3的表达正相关。此外，肺癌耐药细胞与自噬激活有关。所有数据支持Notch3在NSCLC细胞中干细胞样性质增加中的关键作用，这可能与ALDH1A1和CD44的上调以及自噬的激活有关。
Acquired resistance to standard chemotherapy causes treatment failure in patients with local advanced and advanced non-small lung cancer (NSCLC). Cancer stem cells (CSCs) are a small subpopulation within cancer that is thought to be resistant to conventional chemotherapy. The Notch pathway is one of the most intensively studied for putative therapeutic targets of CSCs in solid tumors. In our study, suppression of Notch3 decreased colony and sphere formation of stem-like property in lung cancer cells. In addition, Notch3 expression was demonstrated to be upregulated in the patients with chemoresistance and related to poor prognosis of NSCLC patients. Our results also showed that CSC markers ALDH1A1 and CD44 were highly expressed in NSCLC patients with chemoresistance and these two markers were positively correlated with Notch3 expression in lung cancer specimens from TCGA database. Furthermore, the lung cancer cells with drug resistance were shown to be associated with activation of autophagy. All the data support a crucial role of Notch3 in the increase of stem-like property in NSCLC cells that might be associated with upregulation of ALDH1A1 and CD44 and activation of autophagy.