ArticleCell death & disease2013
Zinc chelation: a metallothionein 2A's mechanism of action involved in osteosarcoma cell death and chemotherapy resistance.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- A systematic literature review assessing if genetic biomarkers are predictors for platinum-based chemotherapy response in ovarian cancer patients.European journal of clinical pharmacology · 2020Pooled it
- Genetic aspects of pituitary carcinoma: A systematic review.Medicine · 2016Pooled it
- circVDJ-seq for T cell clonotype detection in single-cell and spatial multi-omics.Genome medicine · 2026Article
- Chemoproteomics-EnabledJournal of the American Chemical Society · 2025Article
- MT2A promotes angiogenesis in chronically ischemic brains through a copper-mitochondria regulatory mechanism.Journal of translational medicine · 2025Article
- Zinc and its binding proteins: essential roles and therapeutic potential.Archives of toxicology · 2025Review
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Metallothionein 3 promotes osteoclast differentiation and survival by regulating the intracellular ZnCell death discovery · 2023Article
- Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells.International journal of molecular sciences · 2022Article
- Metallothionein 2A (MT2A) controls cell proliferation and liver metastasis by controlling the MST1/LATS2/YAP1 signaling pathway in colorectal cancer.Cancer cell international · 2022Article
- The Risk Factors of Blood Cadmium Elevation in Chronic Kidney Disease.International journal of environmental research and public health · 2021Article
- Article
- Hedgehog/GLI1 signaling pathway regulates the resistance to cisplatin in human osteosarcoma.Journal of Cancer · 2021Article
- Impact of metallothionein-knockdown on cisplatin resistance in malignant pleural mesothelioma.Scientific reports · 2020Article
- Kevetrin induces apoptosis in TP53 wild‑type and mutant acute myeloid leukemia cells.Oncology reports · 2020Article
- A FRET-based fluorescent ZnChemical science · 2020Article
- Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide.ACS omega · 2020Article
- The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents.Frontiers in pharmacology · 2020Review
- Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism.JCI insight · 2019Article
- Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia.Cancers · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma is the most common primary tumor of bone occurring in children and adolescents. The histological response to chemotherapy represents a key clinical factor related to survival. We previously showed that statins exhibit antitumor effects in vitro, inducing apoptotic cell death, reducing cell migration and invasion capacities and strengthening cytotoxic effects in combination with standard drugs. Comparative transcriptomic analysis between control and statin-treated cells revealed strong expression of several genes, including metallothionein (MT) 2A. MT2A overexpression by lentiviral transduction reduced bioavailable zinc levels, an effect associated with reduced osteosarcoma cell viability and enhanced cell differentiation. In contrast, MT2A silencing did not modify cell viability but strongly inhibited expression of osteoblastic markers and differentiation process. MT2A overexpression induced chemoresistance to cytotoxic drugs through direct chelation of platinum-containing drugs and indirect action on p53 zinc-dependent activity. In contrast, abrogation of MT2A enhanced cytotoxic action of chemotherapeutic drugs on osteosarcoma cells. Finally, clinical samples derived from chemonaive biopsies revealed that tumor cells expressing low MT2A levels correspond to good prognostic (good responder patients with longer survival rate), whereas high MT2A levels were associated with adverse prognosis (poor responder patients). Taken together, these data show that MT2A contributes to chemotherapy resistance in osteosarcoma, an effect partially mediated by zinc chelation. The data also suggest that MT2A may be a potential new prognostic marker for osteosarcoma sensitivity to chemotherapy.
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