Inhibition of yes-associated protein suppresses migration, invasion, and metastasis in non-small cell lung cancer in vitro and in vivo
Inhibition of yes-associated protein suppresses migration, invasion, and metastasis in non-small cell lung cancer in vitro and in vivo
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DOI：
10.1007/s10238-021-00738-4
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发表时间：
2021-07
影响因子：
4.6
通讯作者：
T. Takeda;M. Tsubaki;Shuji Genno;T. Matsuda;Yuuta Yamamoto;A. Kimura;Nao Shimizu;S. Nishida
中科院分区：
文献类型：
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作者：
T. Takeda;M. Tsubaki;Shuji Genno;T. Matsuda;Yuuta Yamamoto;A. Kimura;Nao Shimizu;S. Nishida
非小细胞肺癌(NSCLC)是一种高度侵袭性的癌症，是最常见的恶性肿瘤之一。非小细胞肺癌的转移是治疗失败和癌症相关死亡的主要原因。YAP是一种转录共激活因子，受进化上保守的河马信号通路调节，该通路调节器官的大小、生长和再生。YAP在多种恶性肿瘤中高度表达。此外，YAP促进各种类型癌症的肿瘤启动和/或进展。然而，目前还不清楚YAP是否促进了NSCLC的转移，是否可以作为一个有用的治疗靶点。在这里，我们研究了YAP水平是否与NSCLC细胞的转移表型相关，并作为有用的治疗靶点。我们发现，在非小细胞肺癌细胞系中，高水平的YAP与高细胞迁移、侵袭和转移有关。此外，YAPsiRNA还降低了NSCLC细胞的迁移和侵袭能力。此外，用于治疗症状性息肉状脉络膜血管病变的药物维替泊芬可以减少YAP的表达，并抑制NSCLC细胞的迁移、侵袭和转移。因此，本研究表明，靶向YAP可能为开发抗NSCLC转移的治疗药物提供了一条新的途径，维替普芬具有治疗转移性NSCLC的潜在分子治疗策略。
Non-small cell lung cancer (NSCLC) is a highly aggressive cancer with one of the most prevalent malignant tumors. Metastasis in NSCLC is the major cause of treatment failure and cancer-related deaths. Yes-associated protein (YAP) is a transcriptional coactivator regulated by the evolutionarily conserved Hippo signaling pathway that regulates organ size, growth, and regeneration. YAP is highly expressed in several malignant tumor types. Furthermore, YAP promotes tumor initiation and/or progression in various types of cancer. However, it is unclear whether YAP contributes to the metastasis in NSCLC and serves as a useful therapeutic target. Here, we investigated whether levels of YAP correlate with metastatic phenotype in NSCLC cells and serve as a useful therapeutic target. We found that high levels of YAP associate with high cell migration, invasion, and metastasis in NSCLC cell lines. Furthermore,YAPsiRNA decreased the migration and invasion in NSCLC cells. Additionally, verteporfin, an agent used for the treatment of symptomatic polypoidal choroidal vasculopathy, decreased the expression of YAP and inhibited migration, invasion, and metastasis in NSCLC cells. Thus, the study suggests that targeting YAP may present a new avenue to develop therapeutics against metastasis in NSCLC and that verteporfin has potential molecular therapeutic strategy for the treatment of metastatic NSCLC.