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

Trace element geochemistry as a tool for interpreting microbialites

Microbialites are critical for documenting early life on earth and-possibly elsewhere in the solar system. However, criteria for microbialite identification are controversial. Trace element geochemistry provides two types of information that aid interpretation of putative microbialites. Firstly, because most microbialites-consist of hydrogenous precipitates, trace elements can be used to investigate the fluids in which the structures formed, thus aiding identification of environments of formation. For example, rare earth elements preserved in microbialites have proven very useful in discriminating depositional environments. Secondly, microbes utilize and concentrate a wide range of elements, including many metals. Preservation of such elemental enrichments may provide a valuable biosignature. Although research in this field is relatively young, high precision, in situ measurement of metals in microbialites using techniques such as laser ablation-inductively coupled plasma-mass spectrometry, now with spatial mapping, have identified consistent enrichments in biologically important metals in microbialites. Hence, trace element studies are finding increasing utility in studying microbialites, and so long as diagenesis and the degree to which specific precipitates represent microenvironments are taken into account, trace element inventories may provide important information about depositional settings and, potentially, metabolic processes within biofilms