Browsing by Author "Mukhtarova, Gunel"

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    Megalin (Lrp2) Expression Patterns in Prostate Cancer Stem Cells and Metastatic Subtypes: Implications for Tumor Progression and Metabolism
    (Wiley, 2025) Mukhtarova, Gunel; Murat, Aysegul; Biray Avci, Cigir; Acikgoz, Eda; Aktug, Huseyin; Oktem, Gulperi
    Background Megalin (LRP2) is a multifunctional endocytic receptor whose role in prostate cancer (PCa), particularly in cancer stem cells (CSCs) and metastatic progression, remains largely unexplored.Methods We analyzed LRP2 mRNA and protein expression in DU-145, PC-3, and RWPE1 cells and their CD133high/CD44high CSCs via qRT-PCR and immunofluorescence, in both 2D and 3D cultures. Public RNA-seq data (TCGA, WCDT-MCRPC) were used to assess LRP2, CD133, and CD44 across normal, primary, and metastatic tumors. Gene Set Enrichment Analysis (GSEA) and correlation with AR, VDR, and stemness genes were performed.Result LRP2 was significantly upregulated in DU-145 cells and CSCs in the 3D culture system. In contrast, PC-3 CSCs showed reduced LRP2 expression. In clinical datasets, LRP2 was highest in metastatic tumors (log2FC = 3.58), with bone (M1B) and other parts of the body (M1C) subtypes exhibiting elevated levels compared to primary tumors. CD133 was consistently downregulated in metastases. GSEA highlighted LRP2 involvement in lipid, retinoid, and steroid metabolism. LRP2 correlated positively with VDR and negatively with AR in M1C tumors.Conclusion LRP2 shows subtype-specific expression patterns in PCa, with elevated levels in DU-145 CSCs and metastatic tumors. Its link to metabolic pathways and inverse relationship with AR suggest a potential role in therapy resistance and metastasis.
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    Sonic Hedgehog Signaling Is Associated With Resistance To Zoledronic Acid in Cd133high/Cd44high Prostate Cancer Stem Cells
    (Springer, 2021) Acikgoz, Eda; Mukhtarova, Gunel; Alpay, Araz; Avci, Cigir Biray; Bagca, Bakiye Goker; Oktem, Gulperi
    Cancer stem cells (CSCs) are a unique population that has been linked to drug resistance and metastasis and recurrence of prostate cancer. The sonic hedgehog (SHH) signal regulates stem cells in normal prostate epithelium by affecting cell behavior, survival, proliferation, and maintenance. Aberrant SHH pathway activation leads to an unsuitable expansion of stem cell lineages in the prostate epithelium and the transformation of prostate CSCs (PCSCs). Zoledronic acid (ZOL), one of the third-generation bisphosphonates, effectively prevented bone metastasis and treated advanced prostate cancer despite androgen deprivation therapy. Despite strong evidence for the involvement of the SHH in human PCSCs survival and drug resistance, the roles of SHH in the PCSCs-related resistance to ZOL remain to be fully elucidated. The present study aimed to investigate the role of the SHH pathway in ZOL resistance of PCSCs in 2D and three 3D cell culture conditions. For this purpose, we isolated CD133(high)/ CD44(high) PCSCs using a flow cytometer. Following ZOL treatment, mRNA and protein expressions of the components of the SHH signaling pathway in PCSCs and non-CSCs were analyzed using qRT-PCR and Immunofluorescence staining, respectively. Our finding suggested that SHH signaling may be activated by different mechanisms that lead to avoidance of the inhibition effect of ZOL. Thereby, SHH pathways may be associated with the resistance to ZOL developed by prostate CSCs. Inhibition of CSCs-related SHH signaling along with ZOL treatment should be considered to achieve improvement in survival or delayed treatment failure and prevention of the CSCs-related drug resistance.