Division of labor between YAP and TAZ in non-small cell lung cancer [RNA]

The paralogous transcriptional cofactors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ, also called WWTR1), the main downstream effectors of the Hippo signal transduction pathway, are emerging as pivotal determinants of malignancy in lung cancer. Traditionally, studies have tended to consider YAP and TAZ as functionally redundant transcriptional cofactors, with similar biological impact. However, there is growing evidence that each of them also possesses distinct attributes. We sought to systematically characterize the division of labor between YAP and TAZ in non-small cell lung cancer (NSCLC), the most common histological subtype of lung cancer. We showed that the two paralogs orchestrate non-overlapping transcription programs in this cancer type. To compare YAP and TAZ impact on the transcriptome of lung cancer-derived cells, we performed RNA-sequencing (RNA-seq) analysis following siRNA-mediated transient knockdown of either YAP or TAZ. Human NSCLC-derived H1299and A549 cells were transiently transfected with siRNA SMARTpools targeting either YAP (siYAP) or TAZ (siTAZ) or with control siRNA; RNA was extracted 48 hours later and subjected to RNA-seq analysis.