ArticleMolecular cancer2013
PTEN loss mediated Akt activation promotes prostate tumor growth and metastasis via CXCL12/CXCR4 signaling.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 3 of them syntheses that pooled it.
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Who cites it
89 citing papers in PubMed, 3 syntheses or guidelines pooled it, 147 citations in OpenAlex.
- A meta-analysis for CXCR4 as a prognostic marker and potential drug target in non-small cell lung cancer.Drug design, development and therapy · 2015Pooled it
- Clinicopathological significance of CXCR4 in non-small cell lung cancer.Drug design, development and therapy · 2015Pooled it
- Genetics of breast cancer bone metastasis: a sequential multistep pattern.Clinical & experimental metastasis · 2014Pooled it
- Ineffectiveness of immune checkpoint inhibitors in prostate cancer: is it just a question of '-mabs'?The Journal of pathology · 2026Review
- Network and Gene Set Enrichment Analysis of Adipokine Drivers of Prostate Cancer; Unravelling the Mechanistic Link Between Excess Adiposity and Prostate Cancer Risk.Cancer medicine · 2026Article
- CREPT is required for the metastasis of triple-negative breast cancer through a co-operational-chromatin loop-based gene regulation.Molecular cancer · 2025Article
- Anti-PD1 prolongs the response of PI3K and farnesyl transferase inhibition in HRAS- and PIK3CA-mutant head and neck cancers.Neoplasia (New York, N.Y.) · 2025Article
- Role of multi‑omics in advancing the understanding and treatment of prostate cancer (Review).Molecular medicine reports · 2025Review
- Bone Marrow Failure in Prostate Cancer: A Rare Case Initially Disguised as Thrombotic Thrombocytopenic Purpura.Cureus · 2025Article
- The role of immune cells and immune related genes in the tumor microenvironment of papillary thyroid cancer and their significance for immunotherapy.Scientific reports · 2024Article
- PTEN loss in glioma cell lines leads to increased extracellular vesicles biogenesis and PD-L1 cargo in a PI3K-dependent manner.bioRxiv : the preprint server for biology · 2024Article
- Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective.International journal of molecular sciences · 2024Review
- NDR1/FBXO11 promotes phosphorylation-mediated ubiquitination of β-catenin to suppress metastasis in prostate cancer.International journal of biological sciences · 2024Article
- The Role of Cytokines in Activation of Tumour-promoting Pathways and Emergence of Cancer Drug Resistance.Current topics in medicinal chemistry · 2024Review
- Obesity and prostate cancer - microenvironmental roles of adipose tissue.Nature reviews. Urology · 2023Review
- Myricetin: a potential plant-derived anticancer bioactive compound-an updated overview.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- [MiR-30e-5p overexpression promotes proliferation and migration of colorectal cancer cells by activating the CXCL12 axisNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- A Novel Interaction between Chemokine and Phosphoinositide Signaling in Metastatic Prostate Cancer.Medical research archives · 2023Article
- Cancer-associated fibroblasts contribute to cancer metastasis and apoptosis resistance in human ovarian cancer via paracrine SDF-1α.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Extracellular Vesicles and Their Zeta Potential as Future Markers Associated with Nutrition and Molecular Biomarkers in Breast Cancer.International journal of molecular sciences · 2023Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
introductionThe chemokine CXCL12, also known as SDF-1, and its receptor, CXCR4, are overexpressed in prostate cancers and in animal models of prostate-specific PTEN deletion, but their regulation is poorly understood. Loss of the tumor suppressor PTEN (phosphatase and tensin homolog) is frequently observed in cancer, resulting in the deregulation of cell survival, growth, and proliferation. We hypothesize that loss of PTEN and subsequent activation of Akt, frequent occurrences in prostate cancer, regulate the CXCL12/CXCR4 signaling axis in tumor growth and bone metastasis.
methodsMurine prostate epithelial cells from PTEN+/+, PTEN+/-, and PTEN-/- (prostate specific knockdown) mice as well as human prostate cancer cell lines C4-2B, PC3, and DU145 were used in gene expression and invasion studies with Akt inhibition. Additionally, HA-tagged Akt1 was overexpressed in DU145, and tumor growth in subcutaneous and intra-tibia bone metastasis models were analyzed.
resultsLoss of PTEN resulted in increased expression of CXCR4 and CXCL12 and Akt inhibition reversed expression and cellular invasion. These results suggest that loss of PTEN may play a key role in the regulation of this chemokine activity in prostate cancer. Overexpression of Akt1 in DU145 resulted in increased CXCR4 expression, as well as increased proliferation and cell cycle progression. Subcutaneous injection of these cells also resulted in increased tumor growth as compared to neo controls. Akt1 overexpression reversed the osteosclerotic phenotype associated with DU145 cells to an osteolytic phenotype and enhanced intra-osseous tumor growth.
conclusionsThese results suggest the basis for activation of CXCL12 signaling through CXCR4 in prostate cancer driven by the loss of PTEN and subsequent activation of Akt. Akt1-associated CXCL12/CXCR4 signaling promotes tumor growth, suggesting that Akt inhibitors may potentially be employed as anticancer agents to target expansion of PC bone metastases.
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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.