Department of Oncology Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Pathology, Guangdong Medical University, Dongguan, Guangdong, China.
Cancer Med. 2020 Jan;9(1):259-268. doi: 10.1002/cam4.2668. Epub 2019 Nov 6.
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.
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.
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.
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.
我们之前的研究发现 YAP1 可能在小细胞肺癌（SCLC）的多药耐药（MDR）中发挥作用。然而，其潜在机制尚不清楚。
在这项研究中，我们使用免疫组织化学染色来研究 YAP1 的表达，并评估 YAP1 的表达与 SCLC 患者总生存率之间的关系。我们建立了 H69 稳定细胞系，该细胞系过表达组成型激活的 YAP1，以及 H446 稳定细胞系，该细胞系表达显性负性 YAP1。我们进行 CCK-8、流式细胞术分析和体内化疗敏感性实验，以评估 YAP1 在体外和体内对药物敏感性凋亡的作用。
结果表明，YAP1 高表达的患者比 YAP1 低表达的患者生存率更低，疾病分期更晚。YAP1 可能通过抑制 SCLC 的凋亡来诱导 MDR。当 YAP1 过度激活时，YAP1 会诱导 MDR，而在体外和体内抑制 YAP1 时，药物敏感性会增加。CD74 在 SCLC 样本中与 YAP1 显著相关。使用 ISO-1 抑制 CD74 可显著提高药物敏感性。
YAP1 的表达与 SCLC 患者的总生存率和疾病分期显著相关。YAP1 可能在这些患者中发挥重要作用。我们首次报道 YAP1 可在体外和体内诱导 SCLC 的 MDR。CD74 可能参与 YAP1 诱导的 MDR。
