ArticleJournal of experimental & clinical cancer research : CR2021
ZIP10 drives osteosarcoma proliferation and chemoresistance through ITGA10-mediated activation of the PI3K/AKT pathway.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 108 citations in OpenAlex.
- PYCR1 induces ferroptosis via the PI3K/Akt signaling pathway to regulate the proliferation and migration of osteosarcoma.Translational oncology · 2026Article
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Review
- Integrative bioinformatics, network toxicology, and molecular docking elucidate molecular mechanisms of ATBC-induced sarcoma progression with experimental validation.BMC pharmacology & toxicology · 2026Article
- [Overexpression of lncRNA SNHG12 promotes docetaxel resistance of prostate cancer cells by activating PI3K/AKT signalingNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- SLC39A10 drives M2 macrophage polarization and gastric cancer progression through the MAPK14(p38α) pathway.iScience · 2026Article
- TLR4 promotes ESCC progression by driving inflammation and metabolic reprogramming through SLC39A10-mediated zinc homeostasis.Journal of translational medicine · 2026Article
- Veratramine influences the proliferation of human osteosarcoma cells through modulating the PI3K/AKT signaling cascade.Genes & diseases · 2026Article
- TRIM21 promotes K63-linked ubiquitination of ALKBH5 and suppresses cuproptosis via down-regulation of LIAS in esophageal squamous cell carcinoma.Communications biology · 2025Article
- hsa-miR-144-3p and hsa-miR-4262 are exosomal biomarkers and function as tumor suppressors in HCMV positive brain tumor.Future oncology (London, England) · 2025Observational
- HMGB1 and Its Signaling Pathway in Osteosarcoma: Current Advances in Targeted Therapy.Current issues in molecular biology · 2025Review
- ZIP10 as a potential therapeutic target in acute myeloid leukaemia.British journal of haematology · 2025Article
- Review
- DNA dioxygenase TET2 deficiency aggravates sepsis-induced acute lung injury by targeting ITGA10 via the PI3K/AKT signaling pathway.Cellular & molecular biology letters · 2025Article
- ZIP8 modulates ferroptosis to drive esophageal carcinoma progression.Cell death & disease · 2025Article
- cAMP response element-binding protein: A credible cancer drug target.The Journal of pharmacology and experimental therapeutics · 2025Review
- Integrins in Cancer Drug Resistance: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2025Review
- HMGCL activates autophagy in osteosarcoma through β-HB mediated inhibition of the PI3K/AKT/mTOR signaling pathway.Journal of translational medicine · 2025Article
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Research status and prospects of molecular pathological mechanisms and novel therapeutic targets of osteosarcoma: a systematic review.Frontiers in oncology · 2025Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe zinc transporters Zrt- and Irt-related protein (ZIP/SLC39) are overexpressed in human tumors and correlate with poor prognosis; however, their contributions to carcinogenesis and chemoresistance in osteosarcoma (OS) remain unclear.
methodsWe collected 64 OS patient tissues with (n = 12) or without (n = 52) chemotherapy. The expression levels of ZIP10 were measured by immunohistochemistry and applied to prognostic analysis. ZIP10 was knocked down or overexpressed in OS cell lines to explore its effect on proliferation and chemoresistance. RNA sequencing, quantitative real-time PCR, and western blotting analysis were performed to explore ZIP10-regulated downstream target genes. A xenograft mouse model was established to evaluate the mechanisms by which ZIP10 modulates chemoresistance in OS cells.
resultsThe expression of ZIP10 was significantly induced by chemotherapy and highly associated with the clinical outcomes of OS. Knockdown of ZIP10 suppressed OS cell proliferation and chemoresistance. In addition, ZIP10 promoted Zn content-induced cAMP-response element binding protein (CREB) phosphorylation and activation, which are required for integrin α10 (ITGA10) transcription and ITGA10-mediated PI3K/AKT pathway activation. Importantly, ITGA10 stimulated PI3K/AKT signaling but not the classical FAK or SRC pathway. Moreover, overexpression of ZIP10 promoted ITGA10 expression and conferred chemoresistance. Treatment with the CREB inhibitor 666-15 or the PI3K/AKT inhibitor GSK690693 impaired tumor chemoresistance in ZIP10-overexpressing cells. Finally, a xenograft mouse model established by subcutaneous injection of 143B cells confirmed that ZIP10 mediates chemotherapy resistance in OS cells via the ZIP10-ITGA10-PI3K/AKT axis.
conclusionsWe demonstrate that ZIP10 drives OS proliferation and chemoresistance through ITGA10-mediated activation of the PI3K/AKT pathway, which might serve as a target for OS treatment.
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Registered trials
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.