ArticlePloS one2015
TIMP-1 Inhibits Apoptosis in Lung Adenocarcinoma Cells via Interaction with Bcl-2.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- PFN1 Knockdown Aggravates Mitophagy to Retard Lung Adenocarcinoma Initiation and M2 Macrophage Polarization.Molecular biotechnology · 2025Article
- Development and validation of M2 macrophage-related genes in a prognostic model of lung adenocarcinoma based on bulk RNA and ScRNA datasets.Discover oncology · 2025Article
- Bioinformatics analysis-based mining of potential markers for inflammatory bowel disease and their immune relevance.Translational cancer research · 2024Article
- Screening and identification of miR-181a-5p in oral squamous cell carcinoma and functional verification in vivo and in vitro.BMC cancer · 2023Article
- Estimation of hub genes and exploration of multi-omics level alterations in the landscape of lung adenocarcinoma.American journal of translational research · 2023Article
- TIMP-1-expressing breast tumor spheroids for the evaluation of drug penetration and efficacy.Bioengineering & translational medicine · 2022Article
- Article
- Micro RNA-148a Targets Bcl-2 in Patients with Non-Small Cell Lung Cancer.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Mitochondrial Kinases and the Role of Mitochondrial Protein Phosphorylation in Health and Disease.Life (Basel, Switzerland) · 2021Review
- Angiocrine Regulation of Epithelial Barrier Integrity in Inflammatory Bowel Disease.Frontiers in medicine · 2021Review
- Identification of crucial genes associated with lung adenocarcinoma by bioinformatic analysis.Medicine · 2020Observational
- [Effect of tissue inhibitor of metalloproteinase-1 and 2 siRNA on the expression of smad2/3/4 protein in hepatic stellate cells].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Article
- Expression Changes and Impact of the Extracellular Matrix on Etoposide Resistant Human Retinoblastoma Cell Lines.International journal of molecular sciences · 2020Article
- Inflammatory and Fibrogenic Factors in Proliferative Vitreoretinopathy Development.Translational vision science & technology · 2020Review
- Article
- TIMP-1 inhibits proliferation and osteogenic differentiation of hBMSCs through Wnt/β-catenin signaling.Bioscience reports · 2019Article
- TIMP-1 downregulation modulates miR-125a-5p expression and triggers the apoptotic pathway.Oncotarget · 2018Article
- Tissue inhibitor of metalloproteinases 1 enhances rod survival in the rd1 mouse retina.PloS one · 2018Article
- The Inhibitory Effect of C-phycocyanin Containing Protein Extract (C-PC Extract) on Human Matrix Metalloproteinases (MMP-2 and MMP-9) in Hepatocellular Cancer Cell Line (HepG2).The protein journal · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue inhibitors of metalloproteinases (TIMPs) are multifaceted molecules that exhibit properties beyond their classical proteinase inhibitory function. Although TIMP-1 is a known inhibitor of apoptosis in mammalian cells, the mechanisms by which it exerts its effects are not well-established. Our earlier studies using H2009 lung adenocarcinoma cells, implanted in the CNS, showed that TIMP-1 overexpressing H2009 cells (HB-1), resulted in more aggressive tumor kinetics and increased vasculature. The present study was undertaken to elucidate the role of TIMP-1 in the context of apoptosis, using the same lung cancer cell lines. Overexpressing TIMP-1 in a lung adenocarcinoma cell line H2009 resulted in an approximately 3-fold increased expression of Bcl-2, with a marked reduction in apoptosis upon staurosporine treatment. This was an MMP-independent function as a clone expressing TIMP-1 mutant T2G, lacking MMP inhibition activity, inhibited apoptosis as strongly as TIMP1 overexpressing clones, as determined by inhibition of PARP cleavage. Immunoprecipitation of Bcl-2 from cell lysates also co-immunoprecipitated TIMP-1, indicative of an interaction between these two proteins. This interaction was specific for TIMP-1 as TIMP-2 was not present in the Bcl-2 pull-down. Additionally, we show a co-dependency of TIMP-1 and Bcl-2 RNA and protein levels, such that abrogating Bcl-2 causes a downregulation of TIMP-1 but not TIMP-2. Finally, we demonstrate that TIMP-1 dependent inhibition of apoptosis occurs through p90RSK, with phosphorylation of the pro-apoptotic protein BAD at serine 112, ultimately reducing Bax levels and increasing mitochondrial permeability. Together, these studies define TIMP-1 as an important cancer biomarker and demonstrate the potential TIMP-1 as a crucial therapeutic target.
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