Open AccessAldehyde Dehydrogenase 1 (ALDH1) Promotes the Toxicity of TRAIL in Non-Small Cell Lung Cancer Cells via Post-Transcriptional Regulation of MEK-1 Expression
Author(s) -
Tian Shen,
Da-Hua Liu,
Dan Wang,
Fu Ren,
Xia Pu
Publication year - 2018
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000495202
Subject(s) - apoptosis , aldehyde dehydrogenase , cancer research , mapk/erk pathway , cell cycle , biology , cell growth , lung cancer , cancer stem cell , downregulation and upregulation , cancer cell , cell , cancer , chemistry , signal transduction , microbiology and biotechnology , medicine , stem cell , pathology , biochemistry , enzyme , gene , genetics
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.