MDA-9/Syntenin (SDCBP) Is a Critical Regulator of Chemoresistance, Survival and Stemness in Prostate Cancer Stem Cells.

摘要: Despite some progress, treating advanced prostate cancer remains a major clinical challenge. Recent studies have shown that can originate from undifferentiated, rare, stem cell-like populations within the heterogeneous tumor mass, which play seminal roles in formation, maintenance of homeostasis and initiation metastases. These cells possess enhanced propensity toward chemoresistance may serve as prognostic factor for recurrence. extensive studies, selective targeted therapies against these are limited more detailed experiments required to develop novel therapeutics. We now show MDA-9/Syntenin/SDCBP (MDA-9) is critical regulator survival, stemness (PCSCs). MDA-9 regulates expression multiple stem-regulatory genes loss causes complete collapse network PCSCs. Loss also sensitizes PCSCs chemotherapeutics with different modes action, such docetaxel trichostatin-A, suggesting regulate drug resistance. Mechanistically, MDA-9-mediated resistance, survival regulated through activation STAT3. Activated STAT3 protective autophagy well regulation MDR1 on surface demonstrate PCSC via exploiting inter-connected c-myc pathways.