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Alejandro A Granados, Julian M J Pietsch, Sarah A Cepeda-Humerez, Iseabail L Farquhar, Gašper Tkačik, Peter S Swain
Although cells respond specifically to environments, how environmental identity is encoded intracellularly is not understood. Here, we study this organization of information in budding yeast by estimating the mutual information between environmental transitions and the dynamics of nuclear translocation for 10 transcription factors. Our method of estimation is general, scalable, and based on decoding from single cells. The dynamics of the transcription factors are necessary to encode the highest amounts of extracellular information, and we show that information is transduced through two channels: Generalists (Msn2/4, Tod6 and Dot6, Maf1, and Sfp1) can encode the nature of multiple stresses, but only if stress is high; specialists (Hog1, Yap1, and Mig1/2) encode one particular stress, but do so more quickly and for a wider range of magnitudes...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
Anne Serrao, Laura M Jenkins, Alexander A Chumanevich, Ben Horst, Jiaxin Liang, Michael L Gatza, Nam Y Lee, Igor B Roninson, Eugenia V Broude, Karthikeyan Mythreye
CDK8 is a transcription-regulating kinase that controls TGF-β/BMP-responsive SMAD transcriptional activation and turnover through YAP1 recruitment. However, how the CDK8/YAP1 pathway influences SMAD1 response in cancer remains unclear. Here we report that SMAD1-driven epithelial-to-mesenchymal transition (EMT) is critically dependent on matrix rigidity and YAP1 in a wide spectrum of cancer models. We find that both genetic and pharmacological inhibition of CDK8 and its homologous twin kinase CDK19 leads to abrogation of BMP-induced EMT...
May 21, 2018: Oncogene
Fariba Dehghanian, Zohreh Hojati, Fariba Esmaeili, Ali Masoudi-Nejad
The Hippo signaling pathway is identified as a potential regulatory pathway which plays critical roles in differentiation and stem cell self-renewal. Yap1 is a primary transcriptional effector of this pathway. The importance of Yap1 in embryonic stem cells (ESCs) and differentiation procedure remains a challenging question, since two different observations have been reported. To answer this question we used co-expression network and differential co-expression analyses followed by experimental validations. Our results indicate that Yap1 is highly co-expressed with stem cell markers in ESCs but not in differentiated cells (DCs)...
May 15, 2018: Genomics
Rong Yang, Ting-Ting Cai, Xiao-Jun Wu, Yi-Na Liu, Jia He, Xiao-Shi Zhang, Gang Ma, Jiang Li
The expansion of myeloid-derived suppressor cells (MDSCs) correlates with tumorigenesis in colorectal cancer (CRC). Here, we found a significant association between CD33+ MDSC number and YAP1 and PTEN levels in CRC patients (P < 0.05). Moreover, the CD33+ MDSCs, YAP1 and PTEN were identified as predictors for the prognosis of CRC patients (P < 0.05). Notably, CD33+ MDSCs were an independent survival predictor for CRC patients through a Cox model analysis. In vitro data determined that the expression levels of YAP1 and PTEN in CRC-derived cell lines were associated with CRC-derived MDSC induction, and the blockade of YAP1 and PTEN decreased CRC-derived MDSC induction...
May 16, 2018: Immunology
C-Y Huang, Z Han, X Li, H-H Xie, S-S Zhu
OBJECTIVE: To investigate the effects and mechanism of yes-associated protein 1 (YAP1) on thyroid carcinoma cells. MATERIALS AND METHODS: Quantitative Real-time PCR (qRT-PCR) and Western blot assay were used to detect the expression of YAP1 in normal thyroid cells (HT-ori3) and four types of thyroid carcinoma cells: FTC-133, IHH-4, TPC-1 and NPA. The cell lines with the highest expression of YAP1 were selected as the experimental materials. qRT-PCR and Western blot assay were used to detect the interference effect of si-YAP1...
April 2018: European Review for Medical and Pharmacological Sciences
Seh-Hoon Oh, Marzena Swiderska-Syn, Mark L Jewell, Richard T Premont, Anna Mae Diehl
BACKGROUND: Chronic failure of mechanisms that promote effective regeneration of dead hepatocytes causes replacement of functional hepatic parenchyma with fibrous scar and ultimately results in cirrhosis. Therefore, defining and optimizing mechanisms that orchestrate effective regeneration might prevent cirrhosis. We hypothesized that effective regeneration of injured livers requires hepatocytes to evade the growth inhibitory actions of TGF-β since TGF-β signaling inhibits mature hepatocyte growth but drives cirrhosis pathogenesis...
May 11, 2018: Journal of Hepatology
Daniel Grun, Gautam Adhikary, Richard L Eckert
We have identified an epidermal cancer stem (ECS) cell population that drives formation of rapidly growing and highly invasive and vascularized tumors. VEGF-A and neuropilin-1 (NRP-1) are highly expressed in ECS cell tumors and VEGF-A/NRP-1 interaction is required for ECS cell survival and tumor vascularization. We now identify a novel signaling cascade that is triggered by VEGF-A/NRP-1. We show that NRP-1 forms a complex with GIPC1 and α6/β4-integrin to activate FAK/Src signaling, which leads to stabilization of a YAP1/∆Np63α to enhance ECS cell survival, invasion, and angiogenesis...
May 14, 2018: Oncogene
Tingting Lu, Ziming Li, Ying Yang, Wenxiang Ji, Yongfeng Yu, Xiaomin Niu, Qingyu Zeng, Weiliang Xia, Shun Lu
No abstract text is available yet for this article.
May 10, 2018: Cancer Letters
Haijie Ma, Mingshuang Wang, Yunpeng Gai, Huilan Fu, Bin Zhang, Ruoxin Ruan, Kuang-Ren Chung, Hongye Li
This study determines the function of thioredoxin and glutaredoxin systems in the phytopathogenic fungus Alternaria alternata via analyzing mutants from the targeted deletion of genes encoding thioredoxin peroxidase ( Tsa1 ), thioredoxin reductase ( Trr1 ) and glutathione reductase ( Glr1 ). Trr1 , Glr1 but not Tsa1 are required for growth and conidiation. Reduced growth and conidiation seen in the Trr1 or Glr1 deletion mutant can be restored by glutathione. Deletion mutants showing growth inhibition by oxidants are defective for H2 O2 detoxification and induce smaller lesions on citrus leaves...
May 11, 2018: Applied and Environmental Microbiology
Leah A Gates, Guowei Gu, Yue Chen, Aarti D Rohira, Jonathan T Lei, Ross A Hamilton, Yang Yu, David M Lonard, Jin Wang, Shu-Ping Wang, David G Edwards, Philip F Lavere, Jiangyong Shao, Ping Yi, Antrix Jain, Sung Yun Jung, Anna Malovannaya, Shunqiang Li, Jieya Shao, Robert G Roeder, Matthew J Ellis, Jun Qin, Suzanne A W Fuqua, Bert W O'Malley, Charles E Foulds
Approximately 75% of breast cancers are estrogen receptor alpha (ERα)-positive and are treatable with endocrine therapies, but often patients develop lethal resistant disease. Frequent mutations (10-40%) in the ligand-binding domain (LBD) codons in the gene encoding ERα (ESR1) have been identified, resulting in ligand-independent, constitutively active receptors. In addition, ESR1 chromosomal translocations can occur, resulting in fusion proteins that lack the LBD and are entirely unresponsive to all endocrine treatments...
May 11, 2018: Oncogene
Andrew J McKenzie, Stephanie R Hicks, Kathryn V Svec, Hannah Naughton, Zöe L Edmunds, Alan K Howe
There is growing appreciation of the importance of the mechanical properties of the tumor microenvironment on disease progression. However, the role of extracellular matrix (ECM) stiffness and cellular mechanotransduction in epithelial ovarian cancer (EOC) is largely unknown. Here, we investigated the effect of substrate rigidity on various aspects of SKOV3 human EOC cell morphology and migration. Young's modulus values of normal mouse peritoneum, a principal target tissue for EOC metastasis, were determined by atomic force microscopy (AFM) and hydrogels were fabricated to mimic these values...
May 8, 2018: Scientific Reports
Yusuke Takehara, Toshiko Yamochi, Tasuku Nagumo, Tomonari Cho, Fumihiko Urushibara, Kohei Ono, Tomonori Fujii, Naoko Okamoto, Yosuke Sasaki, Sakiko Tazawa, Mayumi Honma, Tomoko Norose, Eisuke Shiozawa, Genshu Tate, Masafumi Takimoto
Gene mutations are involved in the development of malignant mesothelioma. Important mutations have been identified in the genes for cyclin-dependent kinase inhibitor 2A (p16) alternative reading frame, breast cancer-associated protein 1 ( BAP1 ) and neurofibromatosis type 2 ( NF2 ). Previously, the utility of detecting the loss of BAP1 by immunohistochemistry (IHC) and p16-deletion by fluorescence in situ hybridization has been identified in several studies. However, NF2 -associated examinations have not been performed...
May 2018: Oncology Letters
Chloé Philippe, Benoît Pinson, Jim Dompierre, Véronique Pantesco, Benoît Viollet, Bertrand Daignan-Fornier, Michel Moenner
AICAR (Acadesine) is a pharmacological precursor of purine nucleotide biosynthesis with anti-tumoral properties. Although recognized as an AMP mimetic activator of the protein kinase AMPK, the AICAR monophosphate derivative ZMP was also shown to mediate AMPK-independent effects. In order to unveil these AMPK-independent functions, we performed a transcriptomic analysis in AMPKα1/α2 double knockout murine embryonic cells. Kinetic analysis of the cellular response to AICAR revealed the up-regulation of the large tumor suppressor kinases (Lats) 1 and 2 transcripts, followed by the repression of numerous genes downstream of the transcriptional regulators Yap1 and Taz...
May 3, 2018: Neoplasia: An International Journal for Oncology Research
Wuli Zhao, Hong Liu, Junxia Wang, Mengyan Wang, Rongguang Shao
BACKGROUND: A35 is a novel synthetic cyclizing-berberine recently patented as an antitumor compound. Based on its dual targeting topoisomerase (top) activity, A35 might overcome the resistance of single-target top inhibitors and has no cardiac toxicity for not targeting top2β. In this study we further explored the biological effects and mechanisms of A35. METHODS: Antitumor activity of A35 was evaluated by SRB and colony formation assay. G2/M phase arrest (especially M) and first damage of M-phase cells were investigated by flow cytometry, cytogenetic analysis, immunofluorescence, co-immunoprecipitation and WB...
May 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
Cen Cao, Ying Huang, Qingming Tang, Chenguang Zhang, Lei Shi, Jiajia Zhao, Li Hu, Zhewen Hu, Yun Liu, Lili Chen
Co-transplantation of endothelial cells (ECs) and mesenchymal stem cells (MSCs) is an important strategy for repairing complex and large bone defects. However, the ways in which ECs and MSCs interact remain to be fully clarified. We found that forward ephrinB2/Ephs signaling from hBMSCs to hUVECs promoted the tube formation of hUVECs by activating the PI3K/AKT/mTOR pathway. Reverse ephrinB2/Ephs signaling from hUVECs to hBMSCs promoted the proliferation and maintenance of hBMSCs self-renewal via upregulation of OCT4, SOX2, and YAP1...
April 23, 2018: Biomaterials
Hao Jiang, Shuang Liang, Xue-Rui Yao, Yong-Xun Jin, Xing-Hui Shen, Bao Yuan, Jia-Bao Zhang, Nam-Hyung Kim
Laminarin (LMA), a β-glucan mixture with good biocompatibility, improves the growth performance and immune response when used as food additives and nutraceuticals. The aim of the present research was to explore the effects of LMA on porcine early stage embryo development, as well as the underlying mechanisms. The results showed that the developmental competence of porcine early stage embryos was dramatically improved after LMA supplementation during the in vitro culture period. The presence of 20 μg/mL LMA during the in vitro culture period significantly improved cleavage rate, blastocyst formation rates, hatching rate, and total cell number in the blastocyst compared to that in the control group...
April 23, 2018: Theriogenology
Mengxue Yu, Yingzhun Chen, Xuelian Li, Rui Yang, Lijia Zhang, Longtao Huangfu, Nan Zheng, Xiaoguang Zhao, Lifang Lv, Yaozhen Hong, Haihai Liang, Hongli Shan
Yes-associated protein 1 (YAP1) contributes to the development of multiple tumors, but the mechanism underlying YAP1 deregulation in non-small cell lung cancer (NSCLC) remains unclear. By performing immunohistochemistry (IHC) assays, we found that YAP1 was significantly upregulated in NSCLC compared with adjacent tissues; therefore, we sought to elucidate whether the upregulation of YAP1 contributes to NSCLC progression. MTT and transwell assays showed that YAP1 overexpression promoted proliferation, migration, and invasion in the NSCLC cell lines A549 and H460; YAP1 overexpression also promoted the significant differential expression of epithelial-mesenchymal transition (EMT)-related markers...
April 27, 2018: Cell Death & Disease
Hang-Lung Chang, Hsin-An Chen, Oluwaseun Adebayo Bamodu, Kwai-Fong Lee, Yew-Min Tzeng, Wei-Hwa Lee, Jo-Ting Tsai
The cancer stem cells (CSCs) theory recently became a focus of heightened attention in cancer biology, with the proposition that CSCs may constitute an important therapeutic target for effective anticancer therapy, because of their demonstrated role in tumor initiation, chemo-, and radio-resistance. Liver CSCs are a small subpopulation of poorly- or undifferentiated liver tumor cells, implicated in tumorigenesis, metastasis, resistance to therapy and disease relapse, enriched with and associated with the functional markers corresponding to the CSCs-enriched side population (SP), high aldehyde dehydrogenase (ALDH) activity, and enhanced formation of in vitro liver CSCs models, referred to herein as hepatospheres...
April 23, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Masahiro Shibata, Kendall Ham, Mohammad Obaidul Hoque
YAP1 is one of the most important effectors of the Hippo pathway and has crosstalk with other cancer promoting pathways. YAP1 contributes to cancer development in various ways that include promoting malignant phenotypes, expansion of cancer stem cells and drug resistance of cancer cells. Because pharmacologic or genetic inhibition of YAP1 suppresses tumor progression and increases the drug sensitivity, targeting YAP1 may open a fertile avenue for a novel therapeutic approach in relevant cancers. Recent enormous studies have established the efficacy of immunotherapy, and several immune checkpoint blockades are in clinical use or in the phase of development to treat various cancer types...
April 26, 2018: International Journal of Cancer. Journal International du Cancer
Y Shi, B Liu, C-S Wang, C-S Yang
OBJECTIVE: Elevated apoptosis of vascular smooth muscle cell (VSMC) is correlated with the occurrence of aortic dissection (AD). Mammalian ste20-like protein kinase 1 (MST1) is one important component of Hippo-YAP signal pathway for activation and cell apoptosis facilitation. Whether MST1 plays a role in AD pathogenesis is unclear yet. This study established an AD rat model to investigate the role of MST1 in regulating VSMC apoptosis and AD pathogenesis. MATERIALS AND METHODS: Cell apoptosis was compared between AD vascular tissues and normal rats, in addition to Caspase-3 activity, and expression of MST1, p-LATS1, p-YAP1, YAP1...
April 2018: European Review for Medical and Pharmacological Sciences
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