ArticleOncotarget2017
The tissue inhibitor of metalloproteinases-1 (TIMP-1) promotes survival and migration of acute myeloid leukemia cells through CD63/PI3K/Akt/p21 signaling.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- Functional analysis of secreted tissue inhibitor of metalloproteinases-1 from adult human neural stem cells (ahNSCs) for regeneration and neuroprotection.BMB reports · 2025Article
- TIMP-1 enhances Akt and BDNF signaling in neurons to reduce synaptic and cognitive deficits in 5xFAD mouse model of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia.Cell stem cell · 2025Article
- TIMP1 Overexpression in Ovarian Cancer Spheroids: Implications for Prognosis, Resistance, and Metastatic Potential.Cancers · 2025Article
- Shared genetic association between inflammatory bowel disease and acute myeloid leukemia: insights from mendelian randomization and transcriptomic analyses.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Time to relapse in chronic lymphocytic leukemia and DNA-methylation-based biological age.Clinical epigenetics · 2023Article
- Screening and identification of miR-181a-5p in oral squamous cell carcinoma and functional verification in vivo and in vitro.BMC cancer · 2023Article
- Cellular and Molecular Effects of Eribulin in Preclinical Models of Hematologic Neoplasms.Cancers · 2022Article
- Aberrant TIMP-1 overexpression in tumor-associated fibroblasts drives tumor progression through CD63 in lung adenocarcinoma.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Extravesicular TIMP-1 is a non-invasive independent prognostic marker and potential therapeutic target in colorectal liver metastases.Oncogene · 2022Article
- The extracellular matrix of hematopoietic stem cell niches.Advanced drug delivery reviews · 2022Review
- Study on the Correlation between Pain and Cytokine Expression in the Peripheral Blood of Patients with Bone Metastasis of Malignant Cancer Treated Using External Radiation Therapy.Pain research & management · 2022Article
- A Novel Prognostic Model for Acute Myeloid Leukemia Based on Gene Set Variation Analysis.Journal of oncology · 2022Article
- miR-660 promotes liver cancer cell proliferation by targeting PPP2R2A.Experimental and therapeutic medicine · 2021Article
- Surface-bound matrix metalloproteinase-8 on macrophages: Contributions to macrophage pericellular proteolysis and migration through tissue barriers.Physiological reports · 2021Article
- Tumor Growth in the High Frequency Medulloblastoma Mouse Model Ptch1Frontiers in oncology · 2021Article
- Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy.Cell metabolism · 2020Article
- TIMP1 preserves the blood-brain barrier through interacting with CD63/integrinActa pharmaceutica Sinica. B · 2020Article
- Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer.Cells · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We and others have shown that the Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), a member of the inflammatory network exerting pleiotropic effects in the bone marrow (BM) microenvironment, regulates the survival and proliferation of different cell types, including normal hematopoietic progenitor cells. Moreover, TIMP-1 has been shown to be involved in cancer progression. However, its role in leukemic microenvironment has not been addressed. Here, we investigated the activity of TIMP-1 on Acute Myelogenous Leukemia (AML) cell functions. First, we found that TIMP-1 levels were increased in the BM plasma of AML patients at diagnosis. In vitro, recombinant human (rh)TIMP-1 promoted the survival and cell cycle S-phase entry of AML cells. These kinetic effects were related to the downregulation of cyclin-dependent kinase inhibitor p21. rhTIMP-1 increases CXCL12-driven migration of leukemic cells through PI3K signaling. Interestingly, activation of CD63 receptor was required for TIMP-1's cytokine/chemokine activity. Of note, rhTIMP-1 stimulation modulated mRNA expression of Hypoxia Inducible Factor (HIF)-1α, downstream of PI3K/Akt activation. We then co-cultured AML cells with normal or leukemic mesenchymal stromal cells (MSCs) to investigate the interaction of TIMP-1 with cellular component(s) of BM microenvironment. Our results showed that the proliferation and migration of leukemic cells were greatly enhanced by rhTIMP-1 in presence of AML-MSCs as compared to normal MSCs. Thus, we demonstrated that TIMP-1 modulates leukemic blasts survival, migration and function via CD63/PI3K/Akt/p21 signaling. As a "bad actor" in a "bad soil", we propose TIMP-1 as a potential novel therapeutic target in leukemic BM microenvironment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.