ArticleJournal of experimental & clinical cancer research : CR2018
TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a favorable prognosis.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 116 citations in OpenAlex.
- Deciphering lncRNA and circRNA control of autophagy in osteosarcoma mechanisms and clinical translation.Discover oncology · 2026Review
- Natural products reshape osteosarcoma cell fate: promoting cell death.Frontiers in pharmacology · 2026Review
- PHLDA2 in cancer: From molecular mechanisms to therapeutic opportunities.The Journal of pharmacology and experimental therapeutics · 2025Review
- The role of circular RNAs in gastric Cancer: Focusing on autophagy, EMT, and their crosstalk.Biochemistry and biophysics reports · 2025Review
- Regulation of pancreatic cancer cells by suppressing KIN17 through the PI3K/AKT/mTOR signaling pathway.Oncology reports · 2025Article
- Unraveling the role of GPCR signaling in metabolic reprogramming and immune microenvironment of lung adenocarcinoma: a multi-omics study with experimental validation.Frontiers in immunology · 2025Article
- MTHFD1 Regulates Autophagy to Promote Growth and Metastasis in Colorectal Cancer via the PI3K-AKT-mTOR Signaling Pathway.Cancer medicine · 2024Article
- FOSL1 promotes stem cell‑like characteristics and anoikis resistance to facilitate tumorigenesis and metastasis in osteosarcoma by targeting SOX2.International journal of molecular medicine · 2024Article
- Effect of Spicatoside a on Anti-Osteosarcoma MG63 Cells through Reactive Oxygen Species Generation and the Inhibition of the PI3K-AKT-mTOR Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- Construction of a 5-Gene super-enhancer-related signature for osteosarcoma prognosis and the regulatory role of TNFRSF11B in osteosarcoma.Translational oncology · 2024Article
- Article
- Epigenetic modification of PHLDA2 is associated with tumor microenvironment and unfavorable outcome of immune checkpoint inhibitor-based therapies in clear cell renal cell carcinoma.European journal of medical research · 2024Article
- The role of programmed cell death in osteosarcoma: From pathogenesis to therapy.Cancer medicine · 2024Review
- Vitexicarpin Induces Apoptosis and Inhibits Metastatic Properties via the AKT-PRAS40 Pathway in Human Osteosarcoma.International journal of molecular sciences · 2024Article
- Diallyl trisulfide inhibits osteosarcoma 143B cell migration, invasion and EMT by inducing autophagy.Heliyon · 2024Article
- UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment.Nature communications · 2024Article
- Exploration of anti‑osteosarcoma activity of asiatic acid based on network pharmacology andOncology reports · 2024Article
- PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma.Oncology research · 2024Article
- Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis.Open medicine (Warsaw, Poland) · 2024Review
- Heat shock protein family A member 8 serving as a co-activator of transcriptional factor ETV4 up-regulates PHLDA2 to promote the growth of liver cancer.Acta pharmacologica Sinica · 2023Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
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Abstract
backgroundOver the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear.
methodsWe investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing.
resultsWe found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models.
conclusionsOur findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.
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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.