ArticleCancer cell international2021
Hypoxia-induced Tie1 drives stemness and cisplatin resistance in non-small cell lung carcinoma cells.
Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- A novel three-CpG signature for lung adenocarcinoma diagnosis: integrating multi-omics, machine learning, and clinical validation.Translational cancer research · 2026Article
- Integrative Multi-omics Analysis and Mendelian Randomization Reveal Potential Therapeutic Targets and their Stratification in Lung Squamous Cell Carcinoma.Current medicinal chemistry · 2026Article
- HDAC4 Promotes Cancer Stemness in Nonsmall Cell Lung Cancer by Upregulating SLC38A2 Expression via HIF-1α to Enhance Glutamine Metabolism.Analytical cellular pathology (Amsterdam) · 2026Article
- The long non-coding RNA keratin-7 antisense acts as a new tumor suppressor to inhibit tumorigenesis and enhance apoptosis in lung and breast cancers.Cell death & disease · 2023Article
- FLI1 regulates radiotherapy resistance in nasopharyngeal carcinoma through TIE1-mediated PI3K/AKT signaling pathway.Journal of translational medicine · 2023Article
- Tumor microenvironment-induced tumor cell plasticity: relationship with hypoxic stress and impact on tumor resistance.Frontiers in oncology · 2023Review
- The road of NSCLC stem cells toward bone metastases.Bone reports · 2022Article
- An analysis of the significance of the Tre2/Bub2/CDC 16 (TBC) domain protein family 8 in colorectal cancer.Scientific reports · 2022Article
- ITCH facilitates proteasomal degradation of TXNIP in hypoxia- induced lung cancer cells.Thoracic cancer · 2022Article
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9 authors.
Funding
Abstract
backgroundDrug resistance and metastasis involving hypoxic tumor environments and persistent stem cell populations are detrimental to the survival of patients with non-small cell lung carcinoma (NSCLC). Tie1 is upregulated in hypoxia and is believed to counteract the effectiveness of platinum agents by promoting the stemness properties in cells. We have investigated the association of Tie1 with HIF-1α and cisplatin resistance in NSCLC cell lines.
methodsThe expression of Tie1 in a pulmonary microvascular endothelial cell line (HPMEC) and NSCLC cell lines was detected using qRT-PCR and western blotting. The effect of Tie1 on cell stemness and migration was examined by sphere-forming and transwell assays in NSCLC cells with Tie1 silenced. The regulation of Tie1 by HIF-1α was evaluated by a dual-luciferase reporter assay and chromatin immunoprecipitation.
resultsWe found that hypoxia could induce stemness and cisplatin resistance in vitro. Tie1 was expressed at low levels in NSCLC cells when compared with human pulmonary microvascular endothelial cells, however, its expression was increased by hypoxia. Additionally, Tie1 knockdown could reduce stemness properties and increase sensitivity to cisplatin in vitro and in a xenograft mouse model. The promoter of Tie1 contains two predicted hypoxia-response elements (HREs). We mutated both HRE sites and conducted chromatin immune-precipitation and promoter luciferase reporter assays and were able to conclude that the induction of Tie1 by hypoxia was HIF-1α-dependent.
conclusionsOur findings indicated that Tie1 is upregulated in a hypoxic environment by HIF-1α and contributes to tumorigenesis and cisplatin resistance through the promotion of stemness in NSCLC cells.
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