ArticleOncotarget2016
PLA2G16 promotes osteosarcoma metastasis and drug resistance via the MAPK pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- PLAAT2 suppresses gastric cancer progression by facilitating cMyc ubiquitination and inhibiting MEK/ERK signaling.Cell death & disease · 2026Article
- PLA2G16-Mediated Tetracosatetraenoic Acid Rewires Fatty Acid Oxidation to Impair CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inter-Relationship Between Melanoma Vemurafenib Tolerance Thresholds and Metabolic Pathway Choice.Cells · 2025Article
- PLA2G16 expression predicts prognosis and gemcitabine sensitivity in patients with pancreatic cancer.PeerJ · 2025Article
- Bidirectional mechanism of comorbidity of depression and insomnia based on synaptic plasticity.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Enzyme-instructed morphology transformation of mitochondria-targeting peptide for the selective eradication of osteosarcoma.RSC chemical biology · 2022Article
- Functional interplay between long non-coding RNAs and Breast CSCs.Cancer cell international · 2022Review
- Targeting PLA2G16, a lipid metabolism gene, by Ginsenoside Compound K to suppress the malignant progression of colorectal cancer.Journal of advanced research · 2022Article
- A novel lncRNA ROPM-mediated lipid metabolism governs breast cancer stem cell properties.Journal of hematology & oncology · 2021Article
- Identification of key biomarkers and functional pathways in osteosarcomas with lung metastasis: Evidence from bioinformatics analysis.Medicine · 2021Article
- PLA2G16 is a mutant p53/KLF5 transcriptional target and promotes glycolysis of pancreatic cancer.Journal of cellular and molecular medicine · 2020Article
- Delineation of hypoxia-induced proteome shifts in osteosarcoma cells with different metastatic propensities.Scientific reports · 2020Article
- Identification of biomarkers associated with the recurrence of osteosarcoma using ceRNA regulatory network analysis.International journal of molecular medicine · 2019Article
- Relationship between polymorphisms of the lipid metabolism-related gene PLA2G16 and risk of colorectal cancer in the Chinese population.Functional & integrative genomics · 2019Article
- Screening of urine identifies PLA2G16 as a field defect methylation biomarker for prostate cancer detection.PloS one · 2019Article
- miR-142-5p suppresses proliferation and promotes apoptosis of human osteosarcoma cell line, HOS, by targeting PLA2G16 through the ERK1/2 signaling pathway.Oncology letters · 2019Article
- Nanotechnology in orthopedics: a clinically oriented review.BMC musculoskeletal disorders · 2018Review
- PEAK1, acting as a tumor promoter in colorectal cancer, is regulated by the EGFR/KRas signaling axis and miR-181d.Cell death & disease · 2018Article
- Diagnostic investigations of PLA2G16 and CDH11 expression levels as independent prognostic markers of human osteosarcoma.Archives of medical science : AMS · 2017Article
- High expression of PLA2G16 is associated with a better prognosis in HER2-positive breast cancer.Journal of thoracic disease · 2017Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prognosis of metastatic osteosarcoma is dismal and a better understanding of the mechanisms underlying disease progression is essential to improve treatment options and patient outcomes. We previously demonstrated Pla2g16 overexpression in mouse osteosarcoma contributes to metastasis phenotypes and increased expression of PLA2G16 is associated with metastasis and poor prognosis in human tumors. To further examine the mechanisms through which PLA2G16 contributes to human osteosarcoma metastasis and explore the potential of PLA2G16 as a therapeutic target in osteosarcoma, we generated a panel of human osteosarcoma cell lines expressing different levels of PLA2G16. The functional analyses of these cell lines demonstrated high levels of PLA2G16 expression increased osteosarcoma cell migration, invasion, clonogenic survival, and anchorage-independent colony formation. Importantly, this activity was dependent on the phospholipase activity of PLA2G16. Additionally, PLA2G16 overexpression decreased the sensitivity of cells to a panel of chemotherapeutic agents. Analysis of downstream pathways revealed the pro-metastasis functions of PLA2G16 were mediated through the MAPK pathway, as knockdown of PLA2G16 decreased ERK1/2 phosphorylation and pharmacological inhibition of MEK significantly repressed PLA2G16 mediated cell migration and clonogenic survival. Furthermore, PLA2G16 overexpression promoted xenograft tumor growth in vivo, and these tumors exhibit increased ERK1/2 phosphorylation. Lastly, the expression of PLA2G16 is strongly correlated with the increased ERK1/2 phosphorylation in human osteosarcoma samples, and the combined lesions are associated with reduced overall and metastasis-free survival. Collectively, these results demonstrate increased PLA2G16 expression activates the MAPK pathway to enhance osteosarcoma metastasis and may be a novel therapeutic target for these cancers.
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