YAP1 promotes multidrug resistance of small cell lung cancer by CD74-related signaling pathways.

BACKGROUND:Our previous research found that YAP1 may have a role in multidrug resistance (MDR) in small cell lung cancer (SCLC). However, its underlying mechanism is unknown. METHODS:In this study, we investigated the expression of YAP1 using immunohistochemical staining and assessed the relationship between the expression of YAP1 and overall survival in patients with SCLC. We established H69 stable cell lines that overexpressed constitutively active YAP1 and H446 stable cell lines that dominate negative YAP1. We conducted CCK-8, flow cytometric analysis, and in vivo chemosensitivity experiments to evaluate the function of YAP1 in drug sensitivity apoptosis in vitro and in vivo. RESULTS:The results indicated that patients with high YAP1 expression have shorter survival rates and more advanced disease stage than those with low YAP1 expression. YAP1 may induce MDR by inhibiting the apoptosis of SCLC. YAP1 induced MDR when YAP1 was hyperactivated, and drug sensitivity increased when YAP1 was inhibited in vitro and in vivo. CD74 was significantly correlated with YAP1 in SCLC samples. Inhibition of CD74 using ISO-1 increased drug sensitivity significantly. CONCLUSIONS:The expression of YAP1 is significantly correlated with overall survival and disease stage in patients with SCLC. YAP1 may play an important role in these patients. We were the first to report that YAP1 can induce MDR in SCLC in vitro and in vivo. CD74 may be involved in YAP1-induced MDR.

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