Aldehyde Dehydrogenase 1 (ALDH1) Promotes the Toxicity of TRAIL in Non-Small Cell Lung Cancer Cells via Post-Transcriptional Regulation of MEK-1 Expression
Aldehyde Dehydrogenase 1 (ALDH1) Promotes the Toxicity of TRAIL in Non-Small Cell Lung Cancer Cells via Post-Transcriptional Regulation of MEK-1 Expression
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醛脱氢酶 1 (ALDH1) 通过 MEK-1 表达的转录后调节促进 TRAIL 在非小细胞肺癌细胞中的毒性
DOI：
10.1159/000495202
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
夏蒲
中科院分区：
文献类型：
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作者：
夏蒲
背景/目的：基于肿瘤坏死因子相关凋亡诱导配体（TRAIL）的治疗已被用于许多人类癌症。然而，一些肿瘤对TRAIL诱导的细胞死亡具有抗性。乙醛脱氢酶1（ALDH 1）是鉴定CSC的功能性标志物。研究方法：本研究采用殖民地形成实验、AnnexinV/ PI双染及PI染色法检测TRAIL对ALDH 1+非小细胞肺癌（non-small cell lung cancer，NSCLC）细胞增殖、凋亡及细胞周期的影响。此外，我们建立了异种移植小鼠模型，以证实TRAIL在体内的抗肿瘤作用。最后，采用基因芯片和western blot检测ALDH 1 + NSCLC细胞对TRAIL敏感性的深层次机制。结果：TRAIL能抑制ALDH 1 + NSCLC细胞的增殖，诱导细胞凋亡和G1期阻滞。相应地，TRAIL与肿瘤大小减小和ALDH 1+细胞建立的异种移植小鼠模型的有利存活率相关。ALDH 1可通过激活MEK/ERK信号通路，增加ALDH 1 + NSCLC细胞死亡受体（DR）4和DR 5的表达。结论：ALDH 1蛋白可诱导MEK-1 mRNA的稳定性，并通过其3 'UTR促进MEK-1的翻译。
Background/Aim: Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL)-based therapies have been used in many human cancers. However, some tumors are resistant to TRAIL-induced cell death. Aldehyde dehydrogenase 1 (ALDH1) is a functional marker for identification of CSCs. Methods: In this study, we used the colony formation assay, AnnexinV/ PI double staining and PI staining to detect proliferation, apoptosis and cell cycle in ALDH1+ non-small cell lung cancer (NSCLC) cells with TRAIL treatment. In addition, we established xenograft mouse models to confirm the anti-tumor roles of TRAIL in vivo. Finally, gene array and western blot were used to detect the deeper mechanism of the susceptibility of ALDH1+ NSCLC cells to TRAIL. Results: We confirmed that TRAIL could inhibit proliferation, and induce apoptosis and G1 arrest in ALDH1+ NSCLC cells. Correspondingly, TRAIL was associated with decreased tumor size and the favorable survival rate of ALDH1+ cells established xenograft mouse models. ALDH1 could increase the death receptors (DR) 4 and DR5 expression in ALDH1+ NSCLC cells via activating MEK/ERK signaling pathway. Conclusion: ALDH1 protein induced MEK-1 mRNA stability and promoted its translation via its 3’UTR.
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影响因子：
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作者：
Nozaki Y;Tamori S;Inada M;Katayama R;Nakane H;Minamishima O;Onodera Y;Abe M;Shiina S;Tamura K;Kodama D;Sato K;Hara Y;Abe R;Takasawa R;Yoshimori A;Shinomiya N;Tanuma SI;Akimoto K
通讯作者：
Akimoto K
影响因子：
14.9
作者：
Tuszynska I;Magnus M;Jonak K;Dawson W;Bujnicki JM
通讯作者：
Bujnicki JM
BAG3 直接稳定己糖激酶 2 mRNA 并促进胰腺癌细胞中的有氧糖酵解
DOI：
10.1083/jcb.201701064
发表时间：
2017-12-04
期刊：
The Journal of cell biology
影响因子：
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作者：
An MX;Li S;Yao HB;Li C;Wang JM;Sun J;Li XY;Meng XN;Wang HQ
通讯作者：
Wang HQ
透明质酸接枝 PEI-PLGA 纳米颗粒共同递送藤黄酸和 TRAIL 质粒用于治疗三阴性乳腺癌。
影响因子：
6
作者：
Wang S;Shao M;Zhong Z;Wang A;Cao J;Lu Y;Wang Y;Zhang J
通讯作者：
Zhang J
影响因子：
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作者：
Awasthi N;Monahan S;Stefaniak A;Schwarz MA;Schwarz RE
通讯作者：
Schwarz RE