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https://www.readbyqxmd.com/read/27913436/erk-and-p38-mapk-activities-determine-sensitivity-to-pi3k-mtor-inhibition-via-regulation-of-myc-and-yap
#1
Taru Muranen, Laura M Selfors, Julie Hwang, Lisa L Gallegos, Jonathan L Coloff, Carson C Thoreen, Seong A Kang, David M Sabatini, Gordon B Mills, Joan S Brugge
Aberrant activation of the PI3K/mTOR pathway is a common feature of many cancers and an attractive target for therapy, but resistance inevitably evolves as is the case for any cancer cell-targeted therapy. In animal tumor models, chronic inhibition of PI3K/mTOR initially inhibits tumor growth, but over time, tumor cells escape inhibition. In this study, we identified a context-dependent mechanism of escape whereby tumor cells upregulated the proto-oncogene transcriptional regulators c-MYC and YAP1. This mechanism was dependent on both constitutive ERK activity as well as inhibition of the stress kinase p38...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27911857/yap1-regulates-abcg2-and-cancer-cell-side-population-in-human-lung-cancer-cells
#2
Yuyuan Dai, Shu Liu, Wen-Qian Zhang, Yi-Lin Yang, Phillip Hang, Hui Wang, Li Cheng, Ping-Chih Hsu, Yu-Chen Wang, Zhidong Xu, David M Jablons, Liang You
A small population of cancer cells called cancer-initiating cells or cancer stem cells (CSCs) are involved in drug resistance, metastasis, and cancer relapse. Finding pathways that regulate CSC is very important for clinical therapy. ATP-binding cassette sub-family G member 2 (ABCG2) plays a role in side population (SP) cell formation and contributes to chemotherapy resistance in common forms of cancer. Yes-associated protein 1 (YAP1) is a major transcriptional effector of the Hippo pathway, which plays important roles in organ size control and tumorigenesis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27905400/lncbrm-initiates-yap1-signalling-activation-to-drive-self-renewal-of-liver-cancer-stem-cells
#3
Pingping Zhu, Yanying Wang, Jiayi Wu, Guanling Huang, Benyu Liu, Buqing Ye, Ying Du, Guangxia Gao, Yong Tian, Lei He, Zusen Fan
Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC). However, the biology of hepatic CSCs remains largely undefined. Through analysis of transcriptome microarray data, we identify a long noncoding RNA (lncRNA) called lncBRM, which is highly expressed in liver CSCs and HCC tumours. LncBRM is required for the self-renewal maintenance of liver CSCs and tumour initiation. In liver CSCs, lncBRM associates with BRM to initiate the BRG1/BRM switch and the BRG1-embedded BAF complex triggers activation of YAP1 signalling...
December 1, 2016: Nature Communications
https://www.readbyqxmd.com/read/27904394/dose-dependent-protective-and-inductive-effects%C3%A2-of-xanthohumol-on-oxidative-dna-damage-in%C3%A2-saccharomyces-cerevisiae
#4
Daniel O Carvalho, Rui Oliveira, Björn Johansson, Luís F Guido
The effect of xanthohumol, a prenylflavonoid isolated from the hop plant (Humulus lupulus L.), on Saccharomyces cerevisiae DNA oxidative damage and viability was evaluated. Yeast cultures under oxidative stress, induced by H2O2, displayed stronger growth in the presence of 5 mg/L of xanthohumol than cultures with only H2O2. Likewise, DNA damage assessed by the comet assay was significantly lower in cells co-incubated with xanthohumol and H2O2. Accordingly, fluorescence of dichlorofluorescein in cells treated with H2O2 and xanthohumol was considerably lower than in cells exclusively treated with H2O2, indicative of a reactive oxygen species scavenging mechanism and consequent formation of oxidation products, as detected by mass spectrometry...
March 2016: Food Technology and Biotechnology
https://www.readbyqxmd.com/read/27901498/targeting-the-vegf-c-vegfr3-axis-suppresses-slug-mediated-cancer-metastasis-and-stemness-via-inhibition-of-kras-yap1-signaling
#5
REVIEW
Yu-Wen Yeh, Ching-Chia Cheng, Shu-Ting Yang, Chi-Feng Tseng, Ting-Yu Chang, Sin-Ying Tsai, Earl Fu, Chien-Ping Chiang, Li-Chuan Liao, Pei-Wen Tsai, Yung-Luen Yu, Jen-Liang Su
Vascular endothelial growth factor-C (VEGF-C) has been implicated in epithelial-mesenchymal transition (EMT) processes and various human cancers, including skin cancer. Skin cancer is an aggressive human malignancy with increasing incidence worldwide; however, the underlying mechanisms involved in VEGF-C-induced skin cancer stemness and metastasis remain unclear. Here, we report that VEGF-C enhances skin cancer migration, invasion and stemness through Slug up-regulation. Oncomine database analysis indicated that the KRAS/MAPK (mitogen-activated protein kinases) pathway and YAP1 (yes-associated protein 1) expression are positively correlated with metastatic skin cancer...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27864171/mitochondrial-superoxide-dismutase-and-yap1p-act-as-a-signaling-module-contributing-to-ethanol-tolerance-of-yeast-saccharomyces-cerevisiae
#6
Anna N Zyrina, Ekaterina A Smirnova, Olga V Markova, Fedor F Severin, Dmitry A Knorre
: There are two superoxide dismutases in yeast: cytoplasmic and mitochondrial enzymes. Inactivation of the cytoplasmic enzyme, Sod1p, renders the cells sensitive to a variety of stresses while inactivation of the mitochondrial isoform, Sod2p, typically has a weaker effect. One exception is ethanol-induced stress. Here we studied the role of Sod2p in yeast ethanol tolerance. First, we found that repression of SOD2 prevents ethanol-induced relocalization of yeast hydrogen peroxide-sensing transcription factor Yap1p - one of the key stress-resistance proteins...
November 18, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27864128/prostaglandin-e2-activates-yap-and-a-positive-signaling-loop-to-promote-colon-regeneration-following-colitis-but-also-carcinogenesis-in-mice
#7
Han-Byul Kim, Minchul Kim, Young-Soo Park, Intae Park, Tackhoon Kim, Sung-Yeun Yang, Charles J Cho, DaeHee Hwang, Jin-Hak Jung, Sanford D Markowitz, Sung Wook Hwang, Suk-Kyun Yang, Dae-Sik Lim, Seung-Jae Myung
BACKGROUND & AIMS: Prostaglandin E2 (PGE2) is mediator of inflammation that regulates tissue regeneration, but its continual activation has been associated with carcinogenesis. Little is known about factors in the PGE2 signaling pathway that contribute to tumor formation. We investigated whether yes associated protein 1 (YAP1), a transcriptional co-activator in the Hippo signaling pathway, mediates PGE2 function. METHODS: DLD-1 and SW480 colon cancer cell lines were transfected with vectors expressing transgenes or small hairpin RNAs and incubated with recombinant PGE2, with or without pharmacologic inhibitors of signaling proteins, and analyzed by immunoblot, immunofluorescence, quantitative reverse transcription PCR, transcriptional reporter, and proliferation assays...
November 15, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27854329/mir-30e-5p-and-mir-15a-synergistically-regulate-fatty-acid-metabolism-in-goat-mammary-epithelial-cells-via-lrp6-and-yap1
#8
Zhi Chen, Huiling Qiu, Liuan Ma, Jun Luo, Shuang Sun, Kang Kang, Deming Gou, Juan J Loor
MicroRNA (miRNA) regulates the expression of genes and influences a series of biological processes, including fatty acid metabolism. We screened the expression of miRNA in goat mammary glands during peak-lactation and non-lactating ("dry") periods, and performed an in vitro study with goat mammary epithelial cells (GMEC) prior to sequencing analysis. Results illustrated that miR-30e-5p and miR-15a were highly expressed. Utilizing a luciferase reporter assay and Western blot, low-density lipoprotein receptor-related protein 6 (LRP6) and Yes associated protein 1 (YAP1) genes were demonstrated to be a target of miR-30e-5p and miR-15a in GMEC...
November 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27835600/yap1-enhances-cell-proliferation-migration-and-invasion-of-gastric-cancer-in-vitro-and-in-vivo
#9
Dan Sun, Xiaoting Li, Yingjian He, Wenhui Li, Ying Wang, Huan Wang, Shanshan Jiang, Yan Xin
Yes-associated protein 1 (YAP1) plays an important role in the development of carcinomas such as breast, colorectal, and gastric (GC) cancers, but the role of YAP1 in GC has not been investigated comprehensively. The present study strongly suggests that YAP1 and P62 were significantly up-regulated in GC specimens, compared with normal gastric mucosa. In addition, the YAP1high P62high expression was independently associated with poor prognosis in GC (hazard ratio: 1.334, 95% confidence interval: 1.045-1.704, P = 0...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832783/mir-375-induces-docetaxel-resistance-in-prostate-cancer-by-targeting-sec23a-and-yap1
#10
Yuan Wang, Rachel Lieberman, Jing Pan, Qi Zhang, Meijun Du, Peng Zhang, Marja Nevalainen, Manish Kohli, Niraj K Shenoy, Hui Meng, Ming You, Liang Wang
BACKGROUND: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically are centered on docetaxel-based chemotherapy. We previously reported that elevated miR-375 levels were significantly associated with poor overall survival of mCRPC patients. In this study, we evaluated if miR-375 induced chemo-resistance to docetaxel through regulating target genes associated with drug resistance. METHODS: We first compared miR-375 expression level between prostate cancer tissues and normal prostate tissues using data from The Cancer Genome Atlas (TCGA)...
November 10, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27832779/mir-199a-3p-inhibits-cell-proliferation-and-induces-apoptosis-by-targeting-yap1-suppressing-jagged1-notch-signaling-in-human-hepatocellular-carcinoma
#11
Kewei Ren, Tengfei Li, Wenzhe Zhang, Jianzhuang Ren, Zhen Li, Gang Wu
BACKGROUND: miR-199a-3p was significantly downregulated in the majority of human hepatocellular carcinoma (HCC) tissues and HCC cell lines. Yes associated protein 1 (YAP1) was overexpressed in human HCC, which promoted HCC development and progression by upregulating Jagged1 and activating the Notch pathway. We searched potential targets of miR-199a-3p with DIANA, TargetScan and PicTar tools, and found that YAP1 is one of the potential targets. Based on these findings, we speculated that miR-199a-3p might suppress HCC growth by targeting YAP1, downregulating Jagged1 and suppressing the Notch pathway...
November 10, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27812511/transcriptional-control-of-drug-resistance-virulence-and-immune-system-evasion-in-pathogenic-fungi-a-cross-species-comparison
#12
REVIEW
Pedro Pais, Catarina Costa, Mafalda Cavalheiro, Daniela Romão, Miguel C Teixeira
Transcription factors are key players in the control of the activation or repression of gene expression programs in response to environmental stimuli. The study of regulatory networks taking place in fungal pathogens is a promising research topic that can help in the fight against these pathogens by targeting specific fungal pathways as a whole, instead of targeting more specific effectors of virulence or drug resistance. This review is focused on the analysis of regulatory networks playing a central role in the referred mechanisms in the human fungal pathogens Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27809333/yap-tead-and-hnf4%C3%AE-repress-reciprocally-to-regulate-hepatocarcinogenesis
#13
Wang-Yu Cai, Ling-Yun Lin, Han Hao, Sai-Man Zhang, Fei Ma, Xin-Xin Hong, Hui Zhang, Qing-Feng Liu, Guo-Dong Ye, Guang-Bin Sun, Yun-Jia Liu, Sheng-Nan Li, Yuan-Yuan Xie, Jian-Chun Cai, Li Bo-An
: Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, the regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between YAP-TEAD and HNF4α in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells via a ubiquitin proteasome pathway...
November 3, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27793648/shikonin-regulates-c-myc-and-glut1-expression-through-the-mst1-yap1-tead1-axis
#14
Karel Vališ, Pavel Talacko, Valéria Grobárová, Jan Černý, Petr Novák
The general mechanism underlying the tumor suppressor activity of the Hippo signaling pathway remains unclear. In this study, we explore the molecular mechanisms connecting the Hippo signaling pathway with glucose metabolism. We have found that two key regulators of glycolysis, C-MYC and GLUT1, are targets of the Hippo signaling pathway in human leukemia cells. Our results revealed that activation of MST1 by the natural compound shikonin inhibited the expression of GLUT1 and C-MYC. Furthermore, RNAi experiments confirmed the regulation of GLUT1 and C-MYC expression via the MST1-YAP1-TEAD1 axis...
October 25, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27781424/update-on-the-integrated-histopathological-and-genetic-classification-of-medulloblastoma-a-practical-diagnostic-guideline
#15
Torsten Pietsch, Christine Haberler
The revised WHO classification of tumors of the CNS 2016 has introduced the concept of the integrated diagnosis. The definition of medulloblastoma entities now requires a combination of the traditional histological information with additional molecular/genetic features. For definition of the histopathological component of the medulloblastoma diagnosis, the tumors should be assigned to one of the four entities classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma...
November 2016: Clinical Neuropathology
https://www.readbyqxmd.com/read/27780825/transglutaminase-interaction-with-%C3%AE-6-%C3%AE-4-integrin-stimulates-yap1-dependent-%C3%AE-np63%C3%AE-stabilization-and-leads-to-enhanced-cancer-stem-cell-survival-and-tumor-formation
#16
Matthew L Fisher, Candace Kerr, Gautam Adhikary, Daniel Grun, Wen Xu, Jeffrey W Keillor, Richard L Eckert
Transglutaminase 2 (TG2) expression is required for epidermal squamous cell carcinoma cancer stem cell survival. However, the molecular signaling mechanisms triggered by TG2 that mediate this survival action are not well understood. Here we show that TG2 is constitutively expressed in ECS cells where it interacts with α6/β4 integrin to stimulate FAK and Src signaling, leading to phosphoinositide 3 kinase (PI3K) activation of phosphoinositide dependent kinase 1 (PDK1). PDK1 inhibits Hippo signaling, leading to enhanced nuclear accumulation of YAP1, which interacted with and stabilized ΔNp63α to enhance ECS cell spheroid formation, invasion, and migration...
October 25, 2016: Cancer Research
https://www.readbyqxmd.com/read/27771839/transcriptome-and-proteome-oriented-identification-of-dysregulated-eif4g-stat3-and-hippo-pathways-altered-by-pik3ca-h1047r-in-her2-er-positive-breast-cancer
#17
Feixiong Cheng, Junfei Zhao, Ariella B Hanker, Monica Red Brewer, Carlos L Arteaga, Zhongming Zhao
PURPOSE: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in human breast cancer. Furthermore, PIK3CA mutations are commonly associated with resistance to anti-epidermal growth factor receptor 2 (HER2) or anti-estrogen receptor (ER) agents in HER2 or ER positive (HER2(+)/ER(+)) breast cancer. Hence, deciphering the underlying mechanisms of PIK3CA mutations in HER2(+)/ER(+) breast cancer would provide novel insights into elucidating resistance to anti-HER2/ER therapies...
October 22, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27764193/anterior-gradient-2-agr2-induced-epidermal-growth-factor-receptor-egfr-signaling-is-essential-for-murine-pancreatitis-associated-tissue-regeneration
#18
Dariusz Wodziak, Aiwen Dong, Michael F Basin, Anson W Lowe
A recently published study identified Anterior Gradient 2 (AGR2) as a regulator of EGFR signaling by promoting receptor presentation from the endoplasmic reticulum to the cell surface. AGR2 also promotes tissue regeneration in amphibians and fish. Whether AGR2-induced EGFR signaling is essential for tissue regeneration in higher vertebrates was evaluated using a well-characterized murine model for pancreatitis. The impact of AGR2 expression and EGFR signaling on tissue regeneration was evaluated using the caerulein-induced pancreatitis mouse model...
2016: PloS One
https://www.readbyqxmd.com/read/27748436/ergothioneine-biosynthesis-and-functionality-in-the-opportunistic-fungal-pathogen-aspergillus-fumigatus
#19
Kevin J Sheridan, Beatrix Elisabeth Lechner, Grainne O' Keeffe, Markus A Keller, Ernst R Werner, Herbert Lindner, Gary W Jones, Hubertus Haas, Sean Doyle
Ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a trimethylated and sulphurised histidine derivative which exhibits antioxidant properties. Here we report that deletion of Aspergillus fumigatus egtA (AFUA_2G15650), which encodes a trimodular enzyme, abrogated EGT biosynthesis in this opportunistic pathogen. EGT biosynthetic deficiency in A. fumigatus significantly reduced resistance to elevated H2O2 and menadione, respectively, impaired gliotoxin production and resulted in attenuated conidiation...
October 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27734924/study-of-corneal-epithelial-progenitor-origin-and-the-yap1-requirement-using-keratin-12-lineage-tracing-transgenic-mice
#20
Ramesh Babu Kasetti, Subhash Gaddipati, Shifu Tian, Lei Xue, Winston W-Y Kao, Qingxian Lu, Qiutang Li
Key issues in corneal epithelium biology are the mechanism for corneal epithelium stem cells to maintain the corneal epithelial homeostasis and wound healing responses, and what are the regulatory molecular pathways involved. There are apparent discrepancies about the locations of the progenitor populations responsible for corneal epithelial self-renewal. We have developed a genetic mouse model to trace the corneal epithelial progenitor lineages during adult corneal epithelial homeostasis and wound healing response...
October 13, 2016: Scientific Reports
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