The Hippo signaling pathway regulates organ size and plays critical roles in maintaining tissue growth, homeostasis, and regeneration. Dysregulated in a wide spectrum of cancers, in mammals, this pathway is regulated by two key effectors, YAP and TAZ, that may functionally overlap. We found that TAZ promoted liver inflammation and tumor development. The expression of TAZ, but not YAP, in human liver tumors positively correlated with the expression of proinflammatory cytokines. Hyperactivated TAZ induced substantial myeloid cell infiltration into the liver and the secretion of proinflammatory cytokines through a TEAD-dependent mechanism. Furthermore, tumors with hyperactivated YAP and TAZ had distinct transcriptional signatures, which included the increased expression of inflammatory cytokines in TAZ-driven tumors. Our study elucidated a previously uncharacterized link between TAZ activity and inflammatory responses that influence tumor development in the liver.

河马信号通路调节器官的大小，并在维持组织生长，体内稳态和再生中起关键作用。在哺乳动物的多种癌症中异常调节，该途径由两个关键效应子YAP和TAZ调控，它们可能在功能上重叠。我们发现TAZ促进了肝脏炎症和肿瘤的发展。TAZ在人肝肿瘤中的表达与YAP无关，而与促炎细胞因子的表达呈正相关。通过TEAD依赖性机制，高度活化的TAZ诱导髓样细胞大量浸润到肝中，并分泌促炎性细胞因子。此外，具有高度活化的YAP和TAZ的肿瘤具有独特的转录特征，其中包括TAZ驱动的肿瘤中炎性细胞因子的表达增加。