Tissue fibrosis is a pathological condition that is associated with impaired epithelial repair and excessive deposition of extracellular matrix (ECM). Fibrotic lesions increase the risk of cancer in various tissues, but the mechanism linking fibrosis and cancer is unclear. Yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are core components of the Hippo pathway, which have multiple biological functions in the development, homeostasis, and regeneration of tissues and organs. YAP/TAZ act as sensors of the structural and mechanical features of the cell microenvironment. Recent studies have shown aberrant YAP/TAZ activation in both fibrosis and cancer in animal models and human tissues. In fibroblasts, ECM stiffness mechanoactivates YAP/TAZ, which promote the production of profibrotic mediators and ECM proteins. This results in tissue stiffness, thus establishing a feed-forward loop of fibroblast activation and tissue fibrosis. In contrast, in epithelial cells, YAP/TAZ are activated by the disruption of cell polarity and increased ECM stiffness in fibrotic tissues, which promotes the proliferation and survival of epithelial cells. YAP/TAZ are also involved in the epithelial–mesenchymal transition (EMT), which contributes to tumor progression and cancer stemness. Importantly, the crosstalk with transforming growth factor (TGF)-β signaling and Wnt signaling is essential for the profibrotic and tumorigenic roles of YAP/TAZ. In this article, we review the latest advances in the pathobiological roles of YAP/TAZ signaling and their function as a molecular link between fibrosis and cancer.

Purpose: TAZ, also known as WWTR1, has recently been suggested as an oncogene in non-small cell lung cancer (NSCLC). We investigated the clinical relevance of TAZ expression and its functional role in NSCLC tumorigenesis.Experimental Design: We characterized TAZ at the DNA (n ¼ 192), mRNA (n ¼ 196), and protein levels (n ¼ 345) in an NSCLC patient cohort. Gene expression analysis was complemented by a meta-analysis of public datasets (n ¼ 1,382). The effects of TAZ on cell proliferation and cell cycle were analyzed in cell cultures and on tumor growth in mice. TAZ-dependent microarray-based expression profiles in NSCLC cells were combined with molecular profiles in human NSCLC tissues for in silico analysis.Results: Higher TAZ mRNA and protein levels were associated with shorter patient survival. Transduction of TAZ enhanced cell proliferation and tumorigenesis in bronchial epithelial cells, whereas TAZ silencing suppressed cell proliferation and induced cell cycle arrest in NSCLC cells. Microarray and cell culture experiments showed that ErbB ligands (amphiregulin, epiregulin, and neuregulin 1) are downstream targets of TAZ. Our in silico analysis revealed a TAZ signature that substantiated the clinical impact of TAZ and confirmed its relationship to the epidermal growth factor receptor signaling pathway.Conclusion: TAZ expression defines a clinically distinct subgroup of patients with NSCLC. ErbB ligands are suggested to mediate the effects of TAZ on lung cancer progression. Our findings emphasize the tumorigenic role of TAZ and may serve as the basis for new treatment strategies.

The changes in viscoelasticity of natural actomyosin and myosin during thermal gelation were investigated by dynamic viscoelasticity measurements. Thermal gelation of natural actomyosin could be divided into four characteristic temperature ranges. The storage modulus increased considerably in the 32-43"C range, decreased sharply in the 43-52°C range, and then increased again in the .52-80°C range. For the thermal gelation of myosin, the storage modulus increased in two steps at two temperature ranges, i.e., 30-41"C and 51-80°C. An increase in the loss modulus was observed at an early stage of each of the two ranges.

Transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes. Nuclear translocation and activation of TAZ are regulated by multiple mechanisms, including actin cytoskeleton and mechanical forces. TAZ is involved in lung alveolarization during lung development and Taz-heterozygous mice are resistant to bleomycin-induced lung fibrosis. In this study, we explored the roles of TAZ in the pathogenesis of idiopathic pulmonary fibrosis (IPF) through histological analyses of human lung tissues and cell culture experiments. TAZ was highly expressed in the fibroblastic foci of lungs from patients with IPF. TAZ controlled myofibroblast marker expression, proliferation, migration, and matrix contraction in cultured lung fibroblasts. Importantly, actin stress fibers and nuclear accumulation of TAZ were more evident when cultured on a stiff matrix, suggesting a feedback mechanism to accelerate fibrotic responses. Gene expression profiling revealed TAZ-mediated regulation of connective tissue growth factor (CTGF) and type I collagen. Clinical relevance of TAZ-regulated gene signature was further assessed using publicly available transcriptome data. These findings suggest that TAZ is involved in the pathogenesis of IPF through multifaceted effects on lung fibroblasts.

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For the further improvement of the frozen storage of meat and fish meat, deeper know ledge of the mechanism of the freezing denaturation of the muscle proteins as well as better techniques controlling the denaturation are needed. With respect to the denaturation mechanism, various theories or hypotheses have been presented so far, attributing its main cause to the aggregation of the protein molecules1), either through the removal of water2,3), or through the salting-out of the proteins4), to the poisonous effect of the free fatty acids5), to the pH change6), to the formation of formaldehyde7), etc., but the com plicated process of the denaturation brings about difficulties in studying the methods of its control.With a view to obtain information on the denaturation mechanism through the in teraction of the proteins with other substances, as well as to find out some new materials to prevent the denaturation, the authors have been testing the denaturation of a frozen actomyosin preparation of the carp at the presence of a variety of additives, and have found out a preventive effect of monosodium-glutamate (Na-glutamate).The present paper deals with the in vitro model tests for the effect of Na-glutamate on the isolated actomyosin preparation and also with the study on the quality of the "Kamaboko" jelly which is processed from the minced fish meat frozen -stored with and without added Na-glutamate. The latter experiment was performed to check the appli cability of adding Na-glutamate to the Reitosurimi (frozen minced fish meat). Recently, the Reitosurimi became the major material in the Kamaboko manufacture. Moreover, it was aimed that the results with the jelly forming ability as revealed in the quality of Kamaboko could make an information of the wider applicability of this method to the control of the frozen storge denaturation of other foods such as meats and meat products, because the jelly-forming ability of a material is a good index of the state of the actomyosin molecules which makes the major factor of the texture of meats.The tests in 0.05M KCl make a model for the frozen storage of the meat and the

To elucidate the roles of the head and the tail portions of the molecule in the thermal gelation of myosin, the gelation characteristics of heavy mcromyosin (HMM) and of light meromyosin (LMM) were investigated. The aggregation process of HMM corresponded to that of myosin alone in the temperature range above 50°C. Both the dynamic viscoelastic behavior and the aggregation process of LMM agreed fairly well with those of myosin alone in the temperature range up to 45 "C. Therefore, the first development of gel elasticity of myosin was attributable mainly to the tail portion of the molecule and the second was to its head portion.

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