ArticleJournal of experimental & clinical cancer research : CR2019
Cathepsin L-mediated resistance of paclitaxel and cisplatin is mediated by distinct regulatory mechanisms.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Cathepsin L deletion enhances sensitivity to anticancer drugs through Parkin-mediated ubiquitination of Bcl-xL and USP53-induced Survivin destabilization.Cell death and differentiation · 2026Article
- The lysosomal cysteine protease cathepsin L promotes stemness and multidrug resistance of non-small cell lung cancer by targeting HGF activator.Molecular and cellular biochemistry · 2026Article
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Unraveling tumor associated macrophage biology in gynecological cancers for targeted therapy in the single cell omics era.iScience · 2025Review
- From "lysosomal addiction" to targeted therapies: exploiting novel windows in colorectal cancer.European journal of medical research · 2025Review
- CREB Regulates Cisplatin Resistance by Targeting TNKS and KDM6A in NSCLC cell-Derived Tumor Spheroid.International journal of biological sciences · 2025Article
- CENPN suppresses autophagy and increases paclitaxel resistance in nasopharyngeal carcinoma cells by inhibiting the CREB-VAMP8 signaling axis.Autophagy · 2024Article
- Cathepsin L in Lung Adenocarcinoma: Prognostic Significance and Immunotherapy Response Through a Multi Omics Perspective.Cancer informatics · 2024Article
- Reduced Cathepsin L expression and secretion into the extracellular milieu contribute to lung fibrosis in systemic sclerosis.Rheumatology (Oxford, England) · 2023Article
- Cathepsin L promotes chemresistance to neuroblastoma by modulating serglycin.Frontiers in pharmacology · 2022Article
- Differences in the Inhibitory Specificity Distinguish the Efficacy of Plant Protease Inhibitors on Mouse Fibrosarcoma.Plants (Basel, Switzerland) · 2021Article
- Establishing a Macrophage Phenotypic Switch-Associated Signature-Based Risk Model for Predicting the Prognoses of Lung Adenocarcinoma.Frontiers in oncology · 2021Article
- PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation.Biomedicines · 2020Review
- New Classification of Macrophages in Plaques: a Revolution.Current atherosclerosis reports · 2020Review
- miR-16-5p Suppresses Progression and Invasion of OsteosarcomaFrontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCathepsin L (CTSL) is a cysteine protease known to have important roles in regulating cancer cellular resistance to chemotherapy. However mechanism underlying which regulates CTSL-mediated drug resistance remain largely unknown.
methodsWe used NSCLC cell lines: A549, A549/TAX (paclitaxel-resistant), A549/DDP (cisplatin-resistant), H460 and PC9 cells, to evaluate CTSL and drug resistance changes. Tumor specimens from 53 patients with NSCLC and Xenograft models was also utilized to explore the regulatory relationship of CTSL, TGF-β, Egr-1 and CREB.
resultsTGF-β and smad3 were overexpressed only in A549/TAX cells, silencing TGF-β or smad3 in A549/TAX cells decreased the expression of CTSL and enhanced their sensitivity to paclitaxel. Smad3 binds to the Smad-binding-element(SBE) of the CTSL promoter, resulting in increased activity of the CTSL promoter and subsequent CTSL. Egr-1 and CREB were overexpressed only in A549/DDP cells, and silencing Egr-1 or CREB reduced the expression of CTSL and increased cisplatin cytotoxicity. CREB could affect the activity of the CTSL promoter by binding to it. And the potential regulatory factors of CTSL were consistent in vivo and in human lung cancer. These different regulatory mechanisms of CTSL-mediated drug resistance exist in two other NSCLC cell lines.
conclusionCTSL-mediated drug resistance to paclitaxel and cisplatin may be modulated by different mechanisms. The results of our study identified different mechanisms regulating CTSL-mediated drug resistance and identified smad3 as a novel regulator of CTSL.
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Registered trials
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