YES-ASSOCIATED PROTEIN 1 PROMOTES ADENOCARCINOMA GROWTH AND METASTASIS THROUGH ACTIVATION OF THE RECEPTOR TYROSINE KINASE Axl
YES-ASSOCIATED PROTEIN 1 PROMOTES ADENOCARCINOMA GROWTH AND METASTASIS THROUGH ACTIVATION OF THE RECEPTOR TYROSINE KINASE Axl
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YES 相关蛋白 1 通过激活受体酪氨酸激酶 Axl 促进腺癌生长和转移
DOI：
10.1177/039463201202500416
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发表时间：
2012-10-01
影响因子：
3.5
通讯作者：
Guo, X-J.
中科院分区：
文献类型：
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作者：
Cui, Z-L.;Han, F-F.;Guo, X-J.
YAP 1是Hippo通路的核效应子，在多种肿瘤的发生和发展中起重要作用。本研究旨在探讨YAP 1和受体酪氨酸激酶Axl在人肺腺癌中的表达及其临床意义。我们进一步探讨了YAP 1在LAC和胃腺癌（GAC）细胞中介导的可能分子机制。收集了49例人LAC和正常肺组织（NLT）。采用组织芯片免疫组化方法检测YAP 1和Axl的表达，并分析其临床病理特征。采用功能缺失的方法，我们研究了小发夹RNA（shRNA）介导的YAP 1基因敲低对Axl、增殖细胞核抗原（PCNA）和基质金属蛋白酶-9（MMP-9）表达的影响，以及对LAC A549和GAC SGC-7901细胞系增殖活性和侵袭潜力的影响。结果显示，YAP 1和Axl在LAC组织中的表达强阳性率高于NLT组织（87.8%vs.60.8%，P=0.000; 77.6%vs.0.0%，P=0.000），但与LAC患者的年龄、性别、肿瘤大小、TNM分期和淋巴结转移无关（均P>0.05）。斯皮尔曼等级相关分析显示，YAP 1与Axl表达呈正相关。体外敲低雅普可显著下调Axl、PCNA和MMP-9的表达，抑制LAC和GAC细胞的增殖和侵袭。综上所述，与NLT相比，YAP 1和Axl在LAC中高度表达，并且YAP 1的敲低可以通过下调Axl途径来抑制腺癌细胞的增殖和侵袭，这代表了用于治疗癌症的潜在治疗靶标。
Yes-associated protein 1 (YAP1), a nuclear effector of the Hippo pathway, plays an important role in tumorigenesis and progression of multiple cancers. The present study aimed to investigate the clinical significance of YAP1 and receptor tyrosine kinase Axl expression in human lung adenocarcinomas (LAC). We further explored possible molecular mechanisms mediated by YAP1 in LAC and gastric adenocarcinoma (GAC) cells. Forty-nine cases of human LAC and normal lung tissue (NLT) were collected. The expression of YAP1 and Axl was assessed by immunohistochemical assay through tissue microarray procedure and the clinicopathologic characteristics of all patients were analyzed. Using a loss of function approach, we investigated the effects of small hairpin RNA (shRNA)-mediated knockdown of YAP1 on the expression of Axl, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-9 (MMP-9), and the proliferative activities and invasive potential in LAC A549 and GAC SGC-7901 cell lines. As a result, the expression of YAP1 and Axl was found in LAC tissues with higher strong reactivity rate compared to the NLT (87.8% vs.60.8%, P=0.000; 77.6% vs 0.0%, P=0.000), but they did not associate with the age, gender, tumor size, TNM staging or lymph node metastases of LAC patients (each P>0.05). Spearman rank correlation analysis showed a positive correlation between YAP1 and Axl expression. Furthermore, knockdown of YAP in vitro markedly down-regulated the expression of Axl, PCNA and MMP-9, and inhibited the proliferation and invasion of LAC and GAC cells. Taken together, YAP1 and Axl are highly expressed in LAC compared to the NLT, and knockdown of YAP1 may inhibit the proliferation and invasion of adenocarcinoma cells through downregulation of the Axl pathway, representing a potential therapeutic target for the treatment of cancer.