ArticleMolecular and cellular endocrinology2012
The CXCL12/CXCR4 axis promotes ligand-independent activation of the androgen receptor.
Article in Molecular and cellular endocrinology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Implications for clinical prognosis and target discovery of the SWI/SNF complex in genitourinary tumors.Discover oncology · 2026Review
- ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors.The Biochemical journal · 2026Review
- Integrative pan-cancer analysis of dipeptidyl peptidase 4 with clinical andFrontiers in immunology · 2026Article
- Osteoid cell-derived chemokines drive bone-metastatic prostate cancer.Frontiers in oncology · 2023Review
- Review
- Expression profiling of mRNA and functional network analyses of genes regulated by human papilloma virus E6 and E7 proteins in HaCaT cells.Frontiers in microbiology · 2022Article
- Androgen Receptor Activation in Glioblastoma Can Be Achieved by Ligand-Independent Signaling through EGFR-A Potential Therapeutic Target.International journal of molecular sciences · 2021Article
- Post-Translational Modifications That Drive Prostate Cancer Progression.Biomolecules · 2021Review
- Systems Oncology: Bridging Pancreatic and Castrate Resistant Prostate Cancer.Pathology oncology research : POR · 2019Review
- Evaluation of the role of downregulation of SNF5/INI1 core subunit of SWI/SNF complex in clear cell renal cell carcinoma development.American journal of cancer research · 2017Article
- LIM domain only 2 over-expression in prostate stromal cells facilitates prostate cancer progression through paracrine of Interleukin-11.Oncotarget · 2016Article
- G protein-coupled receptor GPR160 is associated with apoptosis and cell cycle arrest of prostate cancer cells.Oncotarget · 2016Article
- 5α-Reductase Type 2 Regulates Glucocorticoid Action and Metabolic Phenotype in Human Hepatocytes.Endocrinology · 2015Article
- Androgen receptor and chemokine receptors 4 and 7 form a signaling axis to regulate CXCL12-dependent cellular motility.BMC cancer · 2015Article
- MicroRNA-31 controls G protein alpha-13 (GNA13) expression and cell invasion in breast cancer cells.Molecular cancer · 2015Article
- Minireview: Tipping the balance: ligand-independent activation of steroid receptors.Molecular endocrinology (Baltimore, Md.) · 2015Review
- CXCL12/CXCR4 signaling counteracts docetaxel-induced microtubule stabilization via p21-activated kinase 4-dependent activation of LIM domain kinase 1.Oncotarget · 2014Article
- Androgen receptor phosphorylation: biological context and functional consequences.Endocrine-related cancer · 2014Review
- Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide.Breast cancer research : BCR · 2014Article
- Mechanisms of action of tasquinimod on the tumour microenvironment.Cancer chemotherapy and pharmacology · 2014Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The molecular mechanisms responsible for the transition of some prostate cancers from androgen ligand-dependent to androgen ligand-independent are incompletely established. Molecules that are ligands for G protein coupled receptors (GPCRs) have been implicated in ligand-independent androgen receptor (AR) activation. The purpose of this study was to examine whether CXCL12, the ligand for the GPCR, CXCR4, might mediate prostate cancer cell proliferation through AR-dependent mechanisms involving functional transactivation of the AR in the absence of androgen. The results of these studies showed that activation of the CXCL12/CXCR4 axis promoted: The nuclear accumulation of both wild-type and mutant AR in several prostate epithelial cell lines; AR-dependent proliferative responses; nuclear accumulation of the AR co-regulator SRC-1 protein; SRC-1:AR protein:protein association; co-localization of AR and SRC-1 on the promoters of AR-regulated genes; AR- and SRC-1 dependent transcription of AR-regulated genes; AR-dependent secretion of the AR-regulated PSA protein; P13K-dependent phosphorylation of AR; MAPK-dependent phosphorylation of SRC-1, and both MAPK- and P13K-dependent secretion of the PSA protein, in the absence of androgen. Taken together, these studies identify CXCL12 as a novel, non-steroidal growth factor that promotes the growth of prostate epithelial cells through AR-dependent mechanisms in the absence of steroid hormones. These findings support the development of novel therapeutics targeting the CXCL12/CXCR4 axis as an ancillary to those targeting the androgen/AR axis to effectively treat castration resistant/recurrent prostate tumors.
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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.