The role of YAP1 in small cell lung cancer
The role of YAP1 in small cell lung cancer
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DOI：
10.1007/s13577-022-00669-6
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发表时间：
2022-01
期刊：
影响因子：
4.3
通讯作者：
Haruki Saito;Yuki Tenjin;T. Yamada;S. Kudoh;Noritaka Kudo;M. Sanada;Younosuke Sato;Akira Matsuo-Akira-Ma
中科院分区：
文献类型：
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作者：
Haruki Saito;Yuki Tenjin;T. Yamada;S. Kudoh;Noritaka Kudo;M. Sanada;Younosuke Sato;Akira Matsuo-Akira-Ma
是相关蛋白（雅普）和转录辅激活因子（TAZ，又称WWTR 1）是Hippo通路的核心下游效应子，参与多种生物学过程。雅普和TAZ在非小细胞肺癌（NSCLC）中的致癌作用最近已有报道;然而，它们在SCLC中的作用仍不清楚。采用免疫组化（IHC）法检测肺癌组织中YAP 1的表达，Western blotting（WB）法检测肺癌细胞系中YAP 1的表达。然后使用CRISPR/Cas9的基因组编辑来敲除H69 AR细胞系中的YAP 1基因。对这些细胞进行RNA序列分析、基因本体（GO）分析、WB、细胞计数测定、侵袭测定和异种移植研究以研究YAP 1的生物学作用。免疫组化显示，胰岛素瘤相关蛋白1在大多数情况下（32例中的28例）表达，而只有4例表达YAP 1。在H69 AR细胞中敲除YAP 1，化学诱导的SCLC-Y亚型，降低细胞增殖和侵袭能力，并恢复药物敏感性。异种移植实验表明，敲除YAP 1抑制细胞增殖。肿瘤组织显示神经内分泌标志物的表达和低Ki-67指数。在小细胞肺癌中，YAP 1在细胞增殖、EMT、药物敏感性和神经内分泌分化等生物学功能中发挥重要作用。
Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also known as WWTR1) are core downstream effectors of the Hippo pathway, which is involved in diverse biological processes. The oncogenic effects of YAP and TAZ in non-small cell lung cancer (NSCLC) have recently been reported; however, their roles in SCLC remain unclear. Immunohistochemistry (IHC) on lung cancer tissues and Western blotting (WB) on lung cancer cell lines were performed to examine the expression of YAP1. Genome editing using CRISPR/Cas9 was then used to knockout the YAP1 gene in the H69AR cell line. An RNA-sequence analysis, gene ontology (GO) analysis, WB, cell counting assay, invasion assays, and xenograft studies were conducted on these cells to investigate the biological roles of YAP1. IHC revealed that insulinoma-associated protein 1 was expressed in most cases (28 out of 32 cases), while only four cases expressed YAP1. The knockout of YAP1 in H69AR cells, a chemically induced SCLC-Y subtype, reduced cell proliferation and invasion capacity and restored drug sensitivity. Xenograft assays revealed that the knockout of YAP1 suppressed cell proliferation. Tumor tissues showed the expression of neuroendocrine markers and a low Ki-67 index. In SCLC, YAP1 plays an important role in biological functions, such as cell proliferation, EMT, drug sensitivity, and neuroendocrine differentiation.