RRC ID 63450
Author Horie M, Saito A, Ohshima M, Suzuki HI, Nagase T.
Title YAP and TAZ modulate cell phenotype in a subset of small cell lung cancer.
Journal 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.
Volume 107(12)
Pages 1755-1766
Published 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
Human and Animal Cells Lu-134-A(RCB0466) Lu-134-B(RCB0467) Lu-139(RCB0469)