ArticleClinical & experimental metastasis2020
PTEN loss activates a functional AKT/CXCR4 signaling axis to potentiate tumor growth and lung metastasis in human osteosarcoma cells.
Article in Clinical & experimental metastasis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Warburg-like Metabolic Reprogramming in Endometriosis: From Molecular Mechanisms to Therapeutic Approaches.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeting CXCR4 impaired T regulatory function through PTEN in renal cancer patients.British journal of cancer · 2024Article
- LncRNAs as potential prognosis/diagnosis markers and factors driving drug resistance of osteosarcoma, a review.Frontiers in endocrinology · 2024Review
- Caulis Spatholobi extracts inhibit osteosarcoma growth and metastasis through suppression of CXCR4/PI3K/AKT signaling.Journal of orthopaedic surgery and research · 2023Article
- Article
- Review
- Functional interplay between long non-coding RNAs and the Wnt signaling cascade in osteosarcoma.Cancer cell international · 2021Review
- lncRNA MAGI2-AS3 overexpression had antitumor effect on Hepatic cancer via miRNA-23a-3p/PTEN axis.Food science & nutrition · 2021Article
- HDAC6 inhibitor WT161 performs anti-tumor effect on osteosarcoma and synergistically interacts with 5-FU.Bioscience reports · 2021Article
- Establishment of an Autophagy-Related Clinical Prognosis Model for Predicting the Overall Survival of Osteosarcoma.BioMed research international · 2021Article
- Implication ofMolecular cancer therapeutics · 2020Article
- Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway.Cell death & disease · 2020Article
- Fractalkine/CX3CL1 in Neoplastic Processes.International journal of molecular sciences · 2020Review
- Identification of Potential Therapeutic Targets and Immune Cell Infiltration Characteristics in Osteosarcoma Using Bioinformatics Strategy.Frontiers in oncology · 2020Article
- Long Non-Coding RNA 691 Regulated PTEN/PI3K/AKT Signaling Pathway in Osteosarcoma Through miRNA-9-5p.OncoTargets and therapy · 2020Article
- The Anti-Angiogenic Effects of Anti-Human Immunodeficiency Virus Drugs.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Loss of the tumor suppressor PTEN or activation of chemokine receptor CXCR4 has been demonstrated to associate with OS respectively. However, the signaling mechanism underlying PTEN-mediated antitumor effect remains largely unknown, and the crosstalk between PTEN and CXCR4 in OS has not been investigated. Here, we uncover a PTEN/AKT/CXCR4 pathway nexus in highly tumorigenic and metastatic human 143B OS cells. Loss of PTEN activates AKT/CXCR4 signaling axis and regulates a series of tumor cell behaviors. Notably, ERK is inversely regulated by PTEN and its activation occurs downstream of AKT but upstream of CXCR4, suggesting this kinase to be an important mediator between AKT and CXCR4. In vivo studies show that overexpression of PTEN dramatically attenuates bone destruction, and this inhibition is associated with reduced CXCR4 expression in tumors. CXCR4 inhibitor AMD3100 also markedly suppresses tumor growth in the bone. In addition, PTEN overexpression or AMD3100 substantially inhibits tumor expansion in the lung. Our studies highlight a novel PTEN/AKT/CXCR4 signaling nexus in OS tumor growth and lung metastasis, and provide a strong rationale to consider PTEN restoration or CXCR4 blockade for the treatment of aggressive OS in humans.
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