Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Increasing soil nutrient loads of European semi-natural grasslands strongly alter plant functional diversity independently of species loss

Anthropogenically increased input of nitrogen (N) and phosphorous (P) have led to a severe reduction of plant species richness in European semi-natural grasslands. Although it is well established that this species loss is not trait neutral, a thorough analysis of the effects of nutrient addition on trait based functional diversity and functional composition, independently of species loss, is lacking so far. We compiled data on the plant species abundance (relevé’s) of 279 Nardus grasslands from nine European countries, across a gradient of soil N and P content. Functional diversity (Petchy and Gaston’s FDc, weighted FDc and quadratic entropy) and mean trait composition were calculated for each relevé, based on 21 functional traits. Differences in functional diversity and functional composition were related to differences in soil N, atmospheric N deposition, soil P and pH, while controlling for geographic location and species richness. All functional diversity measures decreased with increasing soil N, with wFDc also decreased by soil P, independent of species loss. This was accompanied by clear shifts in functional trait composition, associated with shifts from below-ground competition for nutrients to above-ground competition for light. This resulted in a decrease in insect-pollinated therophytes and chamaephytes and an increase in long-lived, clonal graminoids and hemicryptophytes under increasing soil N and P. These functional community changes can be expected to alter both ecosystem functioning and service provisioning of the studied grasslands. Our research emphasizes the importance of a reduction of both N and P emission throughout Europe for sustainable conservation of these communities