ArticleOncotarget2013
TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells.
Article in Oncotarget, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Epidemiological Evidence Between Variants in Matrix Metalloproteinases-2, -7, and -9 and Cancer Risk.Frontiers in oncology · 2022Pooled it
- Expression of MMP-2, MMP-9 and TIMP-2 in pituitary tumors and their relationship with cavernous sinus invasion.Endocrine oncology (Bristol, England) · 2025Article
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Article
- The Continuing Saga of Tissue Inhibitor of Metalloproteinase 2: Emerging Roles in Tissue Homeostasis and Cancer Progression.The American journal of pathology · 2023Review
- The Immunohistochemical Expression of Epithelial-Mesenchymal Transition Markers in Precancerous Lesions and Cervical Cancer.International journal of molecular sciences · 2023Article
- Glucosamine-phosphate N-acetyltransferase 1 and its DNA methylation can be biomarkers for the diagnosis and prognosis of lung cancer.Journal of clinical laboratory analysis · 2022Article
- SAHA induce hippo pathway in CCA cells without increasing cell proliferation.Molecular biology reports · 2022Article
- Targeting extracellular Hsp90: A unique frontier against cancer.Frontiers in molecular biosciences · 2022Review
- 22-O-(N-Boc-L-glycine) ester of renieramycin M inhibits migratory activity and suppresses epithelial-mesenchymal transition in human lung cancer cells.Journal of natural medicines · 2021Article
- Pancreatic Lineage Specifier PDX1 Increases Adhesion and Decreases Motility of Cancer Cells.Cancers · 2021Article
- LncRNA TPTEP1 inhibited the proliferation and metastasis of non-small cell lung cancer cells by targeting miR-761/LATS2 axis.American journal of translational research · 2021Article
- Carotenoids in Cancer Metastasis-Status Quo and Outlook.Biomolecules · 2020Review
- TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells.BMC cancer · 2020Article
- TIMP-2 suppresses tumor growth and metastasis in murine model of triple-negative breast cancer.Carcinogenesis · 2020Article
- Schwann Cell Stimulation of Pancreatic Cancer Cells: A Proteomic Analysis.Frontiers in oncology · 2020Article
- An increased level of MiR-222-3p is associated with TMP2 suppression, ERK activation and is associated with metastasis and a poor prognosis in renal clear cell carcinoma.Cancer biomarkers : section A of Disease markers · 2020Article
- Matrisome-Associated Gene Expression Patterns Correlating with TIMP2 in Cancer.Scientific reports · 2019Article
- MicroRNA-130b functions as an oncomiRNA in non-small cell lung cancer by targeting tissue inhibitor of metalloproteinase-2.Scientific reports · 2019Article
- Emphysema phenotypes and lung cancer risk.PloS one · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) plays an essential role in regulating matrix remodeling, cell growth, differentiation, angiogenesis and apoptosis in vitro and in vivo. We have recently shown that TIMP-2-mediated inhibition of tumor growth is independent of matrix metalloproteinase-mediated mechanisms, and is a consequence of modulating both the tumor cells and the tumor microenvironment. In the current study we aim to identify the molecular pathways associated with these effects. We analyzed the transcriptional profile of the human lung cancer cell line A549 upon overexpression of TIMP-2 and Ala+TIMP-2 (mutant that does not inhibit MMP activity), and we found changes in gene expression predominantly related to decreased tumor development and metastasis. Increased E-cadherin expression in response to both TIMP-2 and Ala+TIMP-2 expression was confirmed by real time quantitative RT-PCR and immunoblotting. A549 cells treated with epidermal growth factor (EGF) displayed loss of cobblestone morphology and cell-cell contact, while cells overexpressing TIMP-2 or Ala+TIMP-2 were resistant to EGF-induced morphological changes. Moreover, exogenous treatment with recombinant Ala+TIMP-2 blocked EGF induced down-regulation of E-cadherin. In vivo, immunohistochemistry of A549 xenografts expressing either TIMP-2 or Ala+TIMP-2 demonstrated increased E-cadherin protein levels. More importantly, transcriptional profile analysis of tumor tissue revealed critical pathways associated with effects on tumor-host interaction and inhibition of tumor growth. In conclusion, we show that TIMP-2 promotes an anti-tumoral transcriptional profile in vitro and in vivo, including upregulation of E-cadherin, in A549 lung cancer cells.
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