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https://www.readbyqxmd.com/read/28698296/prkci-promotes-immune-suppression-in-ovarian-cancer
#1
Sharmistha Sarkar, Christopher A Bristow, Prasenjit Dey, Kunal Rai, Ruth Perets, Alejandra Ramirez-Cardenas, Shruti Malasi, Emmet Huang-Hobbs, Monika Haemmerle, Sherry Y Wu, Michael McGuire, Alexei Protopopov, Shan Jiang, Joyce F Liu, Michelle S Hirsch, Qing Chang, Alexander J Lazar, Anil K Sood, Ronny Drapkin, Ronald DePinho, Giulio Draetta, Lynda Chin
A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring PRKC-ι (PRKCI). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called serous tubal intraepithelial carcinoma. Transgenic mouse studies establish PRKCI as an ovarian cancer-specific oncogene. Mechanistically, we show that the oncogenic activity of PRKCI relates in part to the up-regulation of TNFα to promote an immune-suppressive tumor microenvironment characterized by an abundance of myeloid-derived suppressor cells and inhibition of cytotoxic T-cell infiltration...
July 11, 2017: Genes & Development
https://www.readbyqxmd.com/read/28697132/overexpression-of-yes-associated-protein-1-an-independent-prognostic-marker-in-patients-with-pancreatic-ductal-adenocarcinoma-correlated-with-liver-metastasis-and-poor-prognosis
#2
Maria Teresa Salcedo Allende, Jorge Zeron-Medina, Javier Hernandez, Teresa Macarulla, Joaquim Balsells, Xavier Merino, Helena Allende, Josep Tabernero, Santiago Ramon Y Cajal Agüeras
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Overexpression of Yes associated protein 1 (YAP1), a downstream target of Hippo pathway, implicated in regulation of cell growth and apoptosis, has been reported in several human tumor types. The objective of this study was to investigate YAP1 expression in patients with PDAC and its prognostic values. METHODS: We evaluated YAP1 expression in 64 PDAC and 15 chronic pancreatitis (CP) cases and its related pancreatic intraepithelial neoplasia (PanIN) lesions and in 5 control subjects...
August 2017: Pancreas
https://www.readbyqxmd.com/read/28688217/yes-associated-protein-1-promotes-the-differentiation-and-mineralization-of-cementoblast
#3
Beining Yang, Hualing Sun, Fangfang Song, Yanru Wu, Jiawei Wang
Yes-associated protein 1 (YAP1) transcriptional coactivator is a mediator of mechanosensitive signaling. Cementum, which covers the tooth root surface, continuously senses external mechanical stimulation. Cementoblasts are responsible for the mineralization and maturation of the cementum. However, the effect of YAP1 on cementoblast differentiation remains largely unknown. In this study, we initially demonstrated that YAP1 overexpression enhanced the mineralization ability of cementoblasts. YAP1 upregulated the mRNA and protein expression of several cementogenesis markers, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and dentin matrix acidic phosphoprotein 1 (DMP1)...
July 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28677785/microrna-345-inhibits-hepatocellular-carcinoma-metastasis-by-inhibiting-yap1
#4
Hui Zhang, Hui Liu, Huaqiang Bi
MicroRNAs (miRNAs) play critical roles in hepatocellular carcinoma (HCC). However, the expression and biological function of miR-345 in HCC remain unknown. The present study demonstrated that miR-345 expression was reduced in HCC tissues and cell lines. Decreased miR-345 expression was associated with unfavorable clinical features and poor prognosis. In vitro functional assays showed that miR-345 overexpression inhibited the migration and invasion of MHCC-97H cells while miR-345 knockdown promoted metastatic behavior of Hep3B cells...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28677425/ikbke-promotes-glioblastoma-progression-by-establishing-the-regulatory-feedback-loop-of-ikbke-yap1-mir-let-7b-i
#5
Zhimeng Zhang, Jie Lu, Gaochao Guo, Yi Yang, Shicai Dong, Yang Liu, Yang Nan, Yue Zhong, Kai Yu, Qiang Huang
Recently, we have demonstrated that IKBKE (inhibitor of nuclear factor kappa-B kinase subunit epsilon) is overexpressed in human glioblastoma and that inhibition of IKBKE remarkably suppresses the proliferative and invasive behaviour of glioblastoma cells. However, the specific pathogenic molecular mechanism remains to be elucidated. In this study, we verified that IKBKE promotes YAP1 expression via posttranslational modification and accelerates YAP1 translocation to the nucleus for the development of glioblastoma...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28645247/the-correlation-between-poor-prognosis-and-increased-yes-associated-protein-1-expression-in-keratin-19-expressing-hepatocellular-carcinomas-and-cholangiocarcinomas
#6
KyuHo Lee, Kyoung-Bun Lee, Hae Yoen Jung, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Ja-June Jang
BACKGROUND: The Hippo pathway plays a vital role in liver regeneration and development by determining cellular lineage and regulating cell proliferation and apoptosis. In this study, we aimed to assess the role of the Hippo pathway in hepatic carcinogenesis and morphogenesis by examining Yes-associated protein 1 (YAP1) expression in the spectrum of hepatic carcinomas based on cellular lineage. METHODS: We examined 913 primary hepatic carcinomas, including hepatocellular carcinomas (HCCs), combined hepatocellular and cholangiocarcinomas (cHC-CCAs), intrahepatic cholangiocarcinomas (IHCCAs) and perihilar extrahepatic bile duct carcinomas (EHBCAs)...
June 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28628095/a-scaffold-protein-that-chaperones-a-cysteine-sulfenic-acid-in-h2o2-signaling
#7
Antoine Bersweiler, Benoît D'Autréaux, Hortense Mazon, Alexandre Kriznik, Gemma Belli, Agnès Delaunay-Moisan, Michel B Toledano, Sophie Rahuel-Clermont
In Saccharomyces cerevisiae, Yap1 regulates an H2O2-inducible transcriptional response that controls cellular H2O2 homeostasis. H2O2 activates Yap1 by oxidation through the intermediary of the thiol peroxidase Orp1. Upon reacting with H2O2, Orp1 catalytic cysteine oxidizes to a sulfenic acid, which then engages into either an intermolecular disulfide with Yap1, leading to Yap1 activation, or an intramolecular disulfide that commits the enzyme into its peroxidatic cycle. How the first of these two competing reactions, which is kinetically unfavorable, occurs was previously unknown...
June 19, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28627687/microrna%C3%A2-205-acts-as-a-tumor-suppressor-and-directly-targets-yap1-in-glioma
#8
Tao Ji, Xiejun Zhang, Weiping Li
Glioma is the most common form of primary malignant tumor that occurs in the central nervous system. The underlying molecular mechanism of the carcinogenesis and progression of glioma remains to be elucidated. It is well‑established that microRNAs (miRs) are associated with the regulation of glioma initiation and progression, and may represent a novel effective therapeutic strategy for the treatment of glioma. In the present study, the expression, roles and molecular mechanisms of miR‑205 in glioma were investigated...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624413/srsf3-regulated-mir-132-212-controls-cell-migration-and-invasion-by-targeting-yap1
#9
Hye Ree Kim, Su Jin Hwang, Chang Hoon Shin, Kyung Hee Choi, Takbum Ohn, Hyeon Ho Kim
Although SRSF3 (Serine/arginine-rich splicing factor 3) plays a significant role in various biological processes, many of its functions still remain unclear. More particularly, little is known about SRSF3's involvement in the regulation of miRNA. In this report, we found that invasive and migratory abilities were inhibited in SRSF3-silenced U2OS and HeLa cells. We also found that a knockdown of SRSF3 results in a decreased expression level of REST (RE1-silencing transcription factor). The silencing of REST increased the expression of primary miR-132/212 as well as their mature forms...
June 14, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28624193/mir-375-and-doxorubicin-co-delivered-by-liposomes-for-combination-therapy-of-hepatocellular-carcinoma
#10
Yin-Ping Fan, Jia-Zhi Liao, Ya-Qi Lu, De-An Tian, Feng Ye, Peng-Xuan Zhao, Guang-Ya Xiang, Wang-Xian Tang, Xing-Xing He
Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of HCC and drug resistance reversion of DOX. In vitro, L-miR-375/DOX-NPs could deliver DOX and miR-375 efficiently and simultaneously into HCC cells and ensure the successful release of mature miR-375 and DOX...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28616262/rassf1a-methylation-yap1-activation-and-metastasis-a-new-role-for-an-old-foe-in-lung-cancer
#11
EDITORIAL
Min Hee Oh, William W Lockwood
No abstract text is available yet for this article.
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28608501/targeting-hypoxia-mediated-yap1-nuclear-translocation-ameliorates-pathogenesis-of-endometriosis-without-compromising-maternal-fertility
#12
Shih-Chieh Lin, Hsiu-Chi Lee, Pei-Chi Hou, Jhao-Lin Fu, Meng-Hsing Wu, Shaw-Jenq Tsai
Endometriosis is a highly prevalent gynecological disease that severely reduces women's health and quality of life. Ectopic endometriotic lesions have evolved mechanisms to survive in the hypoxic peritoneal microenvironment by regulating the expression of a significant subset of genes. However, the master regulator controlling these genes remains to be characterized. Herein, by using bioinformatics analysis and experimental verification, we identified Yes-Associated Protein 1 (YAP1) as a master regulator of endometriosis...
June 12, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28596500/the-tumor-suppressor-rassf1a-induces-the-yap1-target-gene-ankrd1-that-is-epigenetically-inactivated-in-human-cancers-and-inhibits-tumor-growth
#13
Adriana P Jiménez, Annalena Traum, Thomas Boettger, Holger Hackstein, Antje M Richter, Reinhard H Dammann
The Hippo pathway regulates organ size, growth and comprises several tumor related factors, including the oncoprotein YAP1 and the tumor suppressor RASSF1A. RASSF1A is frequently epigenetically inactivated in cancer. In our study, we analyzed the effect of RASSF1A on the function of YAP1. Expression of YAP1 resulted in the downregulation of several tumor suppressor genes and induction of S-phase. Co-expression with RASSF1A normalized the expression levels of these tumor suppressors and induced a G0-G1 arrest and apoptosis...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28585251/tfe3-rearranged-hepatic-epithelioid-hemangioendothelioma-a-case-report-with-immunohistochemical-and-molecular-study
#14
Fang-Ying Kuo, Hsuan-Ying Huang, Chao-Long Chen, Hock-Liew Eng, Chao-Cheng Huang
A recurrent YAP1-TFE3 gene fusion has been identified in WWTR1-CAMTA1-negative epithelioid hemangioendotheliomas arising in soft tissue, bone, and lung, but not in liver. We present the first case of TFE3-rearranged hepatic epithelioid hemangioendothelioma in a 39-year-old Taiwanese woman. Computed tomography scan revealed multifocal, ill-defined nodules involving both hepatic lobes. She then underwent deceased donor liver transplantation. Histologically, the tumors in the liver explant showed a biphasic growth pattern...
June 6, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28575875/significant-association-of-yap1-and-hspc111-proteins-with-poor-prognosis-in-chinese-gastric-cancer-patients
#15
Shanshan Huang, Lingling Zhu, Yuan Cao, Li Li, Yongtao Xie, Jun Deng, Jianping Xiong
Hippo-YAP1 is a tumor-suppressor signaling pathway that inhibits cell proliferation and accelerates apoptosis. However, the role of YAP1 in gastric cancer (GC) is still in dispute. Ribosomal biogenesis is closely correlated with human malignancies. HBV pre-S2 trans-regulated protein 3 (HSPC111) is a portion of an RNA-dependent complex and plays a crucial role in ribosome biosynthesis. Nevertheless, little is known about the expression and function of this factor in GC. In the present study, we evaluated the significance of YAP1 together with HSPC111 in gastric cancer...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28575156/consequences-of-endogenous-and-exogenous-wnt-signaling-for-development-in-the-preimplantation-bovine-embryo%C3%A2
#16
Paula Tribulo, Beatriz Caetano da Silva Leão, Khoboso C Lehloenya, Gisele Zoccal Mingoti, Peter J Hansen
Although WNT signaling regulates several developmental processes, its specific role during preimplantation development remains unclear. The present aim was to evaluate the consequences of activation and inhibition of β-catenin (CTNNB1) dependent and -independent WNT signaling in the bovine preimplantation embryo. Activation of CTNNB1 mediated WNT signaling by the agonist 2-amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine (AMBMP) and a glycogen synthase kinase 3 (GSK3) inhibitor reduced development to the blastocyst stage...
May 30, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28562356/suppression-of-mir-16-promotes-tumor-growth-and-metastasis-through-reversely-regulating-yap1-in-human-cholangiocarcinoma
#17
Sheng Han, Dong Wang, Guohua Tang, Xinxiang Yang, Chenyu Jiao, Renjie Yang, Yaodong Zhang, Liqun Huo, Zicheng Shao, Zefa Lu, Jiawei Zhang, Xiangcheng Li
BACKGROUND & AIMS: Aberrant expression of microRNAs is associated with many cancers progression. Many studies have shown that miR-16 is down-regulated in many cancers. However, its role in cholangiocarcinoma (CCA) is unknown. METHODS: Quantitative real-time PCR (qRT-PCR) was developed to measure miR-16 expression in CCA tissues and cell lines. CCK-8, colony formation and transwell assays were used to reveal the role of miR-16 in CCA cell proliferation and malignant transformation in vitro...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548934/ikbke-regulates-cell-proliferation-and-epithelial-mesenchymal-transition-of-human-malignant-glioma-via-the-hippo-pathway
#18
Jie Lu, Yi Yang, Gaochao Guo, Yang Liu, Zhimeng Zhang, Shicai Dong, Yang Nan, Zhenyi Zhao, Yue Zhong, Qiang Huang
IKBKE is increased in several types of cancers and is associated with tumour malignancy. In this study, we confirmed that IKBKE promoted glioma proliferation, migration and invasion in vitro. Then, we further discovered that IKBKE increased Yes-associated protein 1 (YAP1) and TEA domain family member 2 (TEAD2), two important Hippo pathway downstream factors, to induce an epithelial-mesenchymal transition (EMT), thus contributing to tumour invasion and metastasis. We also testified that YAP1 and TEAD2 promoted epithelial-mesenchymal transition (EMT) in malignant glioma...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533948/radiosensitization-effect-of-hsa-mir-138-2-3p-on-human-laryngeal-cancer-stem-cells
#19
Ying Zhu, Li-Yun Shi, Yan-Min Lei, Yan-Hong Bao, Zhao-Yang Li, Fei Ding, Gui-Ting Zhu, Qing-Qing Wang, Chang-Xin Huang
BACKGROUND: Treatments that target cancer stem cells play an important role in the controlling and eliminating of tumor initiation as well as in development, progression, and chemotherapy/radiotherapy resistance. In our previous study, we cultured and harvested human laryngeal cancer stem cells (CSCs) and applied microRNA biochips to screen differentially expressed miRNAs that were related to radiation tolerance in irradiated human laryngeal CSCs. According to the predicted genes and pathways of differential miRNAs target, down-regulated expression of hsa-miR-138-2-3p under radiation was thought to play a key role in enhancing the radio-sensitivity in human laryngeal squamous cancer stem cells...
2017: PeerJ
https://www.readbyqxmd.com/read/28504812/overexpression-of-the-yap1-oncogene-in-clear-cell-renal-cell-carcinoma-is-associated-with-poor-outcome
#20
Agnieszka Rybarczyk, Jakub Klacz, Agata Wronska, Marcin Matuszewski, Zbigniew Kmiec, Piotr M Wierzbicki
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC (70-80%). Yes-associated protein 1 (YAP1) protein is a nuclear effector of the Hippo pathway and acts as a transcriptional co-activator of genes involved in the processes of growth and development of tissues. Hippo signaling, with its key kinases, MST2 and large tumor suppressor kinase 1 (LATS1), plays a significant role in the negative regulation of the amount and activity of YAP1 protein. Components of the Hippo pathway and YAP1 levels are frequently dysregulated in a variety of tumors, suggestive of their possible involvement in carcinogenesis...
May 15, 2017: Oncology Reports
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