論文 - 詳細
| RRC ID | 63450 |
|---|---|
| 著者 | Horie M, Saito A, Ohshima M, Suzuki HI, Nagase T. |
| タイトル | YAP and TAZ modulate cell phenotype in a subset of small cell lung cancer. |
| ジャーナル | Cancer Sci |
| Abstract |
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. |
| 巻・号 | 107(12) |
| ページ | 1755-1766 |
| 公開日 | 2016-12-1 |
| DOI | 10.1111/cas.13078 |
| PMID | 27627196 |
| PMC | PMC5198951 |
| MeSH | Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Antineoplastic Agents / pharmacology Cell Adhesion / genetics Cell Line, Tumor Cluster Analysis Drug Resistance, Neoplasm / genetics Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* LIM Domain Proteins / genetics LIM Domain Proteins / metabolism Lung Neoplasms / genetics Lung Neoplasms / metabolism* Lung Neoplasms / pathology* Phenotype* Phosphoproteins / genetics Phosphoproteins / metabolism* Small Cell Lung Carcinoma / genetics Small Cell Lung Carcinoma / metabolism* Small Cell Lung Carcinoma / pathology* Topotecan / pharmacology Trans-Activators Transcription Factors Transcriptional Coactivator with PDZ-Binding Motif Proteins Transcriptome YAP-Signaling Proteins |
| IF | 4.966 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Lu-134-A(RCB0466) Lu-134-B(RCB0467) Lu-139(RCB0469) |