Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells.

摘要: Hyaluronan (HA) is a major glycosaminoglycan in the extracellular matrix whose expression tightly linked to multidrug resistance and tumor progression. In this study we investigated HA-induced interaction between CD44 (a HA receptor) Nanog (an embryonic stem cell transcription factor) both human breast cells (MCF-7 cells) ovarian (SK-OV-3.ipl cells). Using specific primer pair amplify by reverse transcriptase-PCR, detected of transcript lines. addition, our results reveal that binding these promotes protein association with followed activation pluripotent regulators (e.g. Rex1 Sox2). also forms complex "signal transducer activator 3" (Stat-3) nucleus leading Stat-3-specific transcriptional transporter, MDR1 (P-glycoprotein) gene expression. Furthermore, observed HA-CD44 induces ankyrin cytoskeletal protein) resulting efflux chemotherapeutic drugs doxorubicin paclitaxel (Taxol)) chemoresistance cells. Overexpression transfecting cDNA stimulates Stat-3 activation, overexpression, resistance. Down regulation signaling or function (by small interfering RNA repeat domain cDNA) not only blocks HA/CD44-mediated behaviors but enhances chemosensitivity. Taken together, findings suggest targeting Nanog-Stat-3 pathways ankyrin/cytoskeleton may represent novel approach overcome chemotherapy some displaying marker properties during