Open AccessYAP and TAZ modulate cell phenotype in a subset of small cell lung cancer
Author(s) -
Horie Masafumi,
Saito Akira,
Ohshima Mitsuhiro,
Suzuki Hiroshi I.,
Nagase Takahide
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13078
Subject(s) - biology , transcriptome , cancer research , gene knockdown , phenotype , wnt signaling pathway , hippo signaling pathway , cell , gene expression profiling , microarray analysis techniques , cell growth , gene , gene expression , genetics
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 .