YAP and TAZ modulate cell phenotype in a subset of small cell lung cancer.
YAP and TAZ modulate cell phenotype in a subset of small cell lung cancer.
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DOI：
10.1111/cas.13078
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发表时间：
2016-12
期刊：
影响因子：
5.7
通讯作者：
Nagase T
中科院分区：
文献类型：
--
作者：
Horie M;Saito A;Ohshima M;Suzuki HI;Nagase T
小细胞肺癌（SCLC）是一种高度侵袭性和转移性的恶性肿瘤，表现出快速发展的化疗耐药性和高复发率。最近的基因组和转录组研究提供了SCLC的基因组改变和基因表达变化的整个景观。鉴于SCLC的个体间异质性，SCLC的亚型分型可能有助于预测治疗反应和预后。基于SCLC细胞系的转录组数据，我们进行了转录网络定义的SCLC分类，并确定了一个独特的SCLC亚组，其特征在于Hippo通路调节因子Yes相关蛋白（雅普）和具有PDZ结合基序（TAZ）的转录共激活因子（雅普/TAZ亚组）的相对高表达。雅普/TAZ亚组显示贴壁细胞形态、较低表达的无毛鳞片复合物同源物1（ASCL 1）和神经内分泌标志物，以及较高表达的层粘连蛋白和整合素。在许多SCLC细胞系中，雅普敲低引起细胞形态学改变，使人联想到漂浮生长模式，并且微阵列分析揭示了由雅普调控的基因子集，包括Ajuba LIM蛋白（AJUBA）。筋骨草还参与了细胞形态的调节。具有临床意义的是，雅普/TAZ亚组的SCLC细胞系显示出独特的药物敏感性模式。我们的发现揭示了小细胞肺癌的一个亚型与雅普和TAZ表达，并描绘了小细胞肺癌异质性的分子网络。
Small cell lung cancer (SCLC) is a highly aggressive and metastatic malignancy that shows rapid development of chemoresistance and a high rate of recurrence. Recent genome and transcriptome studies have provided the whole landscape of genomic alterations and gene expression changes in SCLC. In light of the inter‐individual heterogeneity of SCLC, subtyping of SCLC might be helpful for prediction of therapeutic response and prognosis. Based on the transcriptome data of SCLC cell lines, we undertook transcriptional network‐defined SCLC classification and identified a unique SCLC subgroup characterized by relatively high expression of Hippo pathway regulators Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ) (YAP/TAZ subgroup). The YAP/TAZ subgroup displayed adherent cell morphology, lower expression of achaete‐scute complex homolog 1 (ASCL1) and neuroendocrine markers, and higher expression of laminin and integrin. YAP knockdown caused cell morphological alteration reminiscent of floating growth pattern in many SCLC cell lines, and microarray analyses revealed a subset of genes regulated by YAP, including Ajuba LIM protein (AJUBA). AJUBA also contributed to cell morphology regulation. Of clinical importance, SCLC cell lines of the YAP/TAZ subgroup showed unique patterns of drug sensitivity. Our findings shed light on a subtype of SCLC with YAP and TAZ expression, and delineate molecular networks underlying the heterogeneity of SCLC.
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DOI：
10.1016/j.cub.2010.02.035
发表时间：
2010-04-13
期刊：
Current biology : CB
影响因子：
--
作者：
Das Thakur M;Feng Y;Jagannathan R;Seppa MJ;Skeath JB;Longmore GD
通讯作者：
Longmore GD
影响因子：
5.5
作者：
Lange, Alexander W.;Sridharan, Anusha;Whitsett, Jeffrey A.
通讯作者：
Whitsett, Jeffrey A.
影响因子：
6.2
作者：
Byers LA;Rudin CM
通讯作者：
Rudin CM
影响因子：
14.9
作者：
Forbes SA;Bindal N;Bamford S;Cole C;Kok CY;Beare D;Jia M;Shepherd R;Leung K;Menzies A;Teague JW;Campbell PJ;Stratton MR;Futreal PA
通讯作者：
Futreal PA
影响因子：
6.4
作者：
Meder L;König K;Ozretić L;Schultheis AM;Ueckeroth F;Ade CP;Albus K;Boehm D;Rommerscheidt-Fuss U;Florin A;Buhl T;Hartmann W;Wolf J;Merkelbach-Bruse S;Eilers M;Perner S;Heukamp LC;Buettner R
通讯作者：
Buettner R