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yap hepatocellular carcinoma

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https://read.qxmd.com/read/30717258/yap-and-taz-heterogeneity-in-primary-liver-cancer-an-analysis-of-its-prognostic-and-diagnostic-role
#1
Matthias Van Haele, Iván M Moya, Ruçhan Karaman, Guy Rens, Janne Snoeck, Olivier Govaere, Frederik Nevens, Chris Verslype, Baki Topal, Diethard Monbaliu, Georg Halder, Tania Roskams
Primary liver cancer comprises a diverse group of liver tumors. The heterogeneity of these tumors is seen as one of the obstacles to finding an effective therapy. The Hippo pathway, with its downstream transcriptional co-activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), has a decisive role in the carcinogenesis of primary liver cancer. Therefore, we examined the expression pattern of YAP and TAZ in 141 patients with hepatocellular carcinoma keratin 19 positive (HCC K19⁺), hepatocellular carcinoma keratin 19 negative (HCC K19- ), combined hepatocellular⁻cholangiocarcinoma carcinoma (cHCC-CCA), or cholangiocarcinoma (CCA)...
February 1, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30700007/high-risk-of-hepatocellular-carcinoma-development-in-fibrotic-liver-role-of-the-hippo-yap-taz-signaling-pathway
#2
REVIEW
Hyuk Moon, Kyungjoo Cho, Sunyeong Shin, Do Young Kim, Kwang-Hyub Han, Simon Weonsang Ro
Liver cancer is the fourth leading cause of cancer-related death globally, accounting for approximately 800,000 deaths annually. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, making up about 80% of cases. Liver fibrosis and its end-stage disease, cirrhosis, are major risk factors for HCC. A fibrotic liver typically shows persistent hepatocyte death and compensatory regeneration, chronic inflammation, and an increase in reactive oxygen species, which collaboratively create a tumor-promoting microenvironment via inducing genetic alterations and chromosomal instability, and activating various oncogenic molecular signaling pathways...
January 29, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30679505/usp7-regulates-hippo-pathway-through-deubiquitinating-the-transcriptional-coactivator-yorkie
#3
Xiaohan Sun, Yan Ding, Meixiao Zhan, Yan Li, Dongqing Gao, Guiping Wang, Yang Gao, Yong Li, Shian Wu, Ligong Lu, Qingxin Liu, Zizhang Zhou
The Hippo pathway plays an important role in organ development and adult tissue homeostasis, and its deregulation has been implicated in many cancers. The Hippo signaling relies on a core kinase cascade culminating in phosphorylation of the transcription coactivator Yorkie (Yki). Although Yki is the key effector of Hippo pathway, the regulation of its protein stability is still unclear. Here, we show that Hippo pathway attenuates the binding of a ubiquitin-specific protease Usp7 to Yki, which regulates Hippo signaling through deubiquitinating Yki...
January 24, 2019: Nature Communications
https://read.qxmd.com/read/30575816/tamoxifen-mechanically-deactivates-hepatic-stellate-cells-via-the-g-protein-coupled-estrogen-receptor
#4
Ernesto Cortes, Dariusz Lachowski, Alistair Rice, Stephen D Thorpe, Benjamin Robinson, Gulcen Yeldag, David A Lee, Leo Ghemtio, Krista Rombouts, Armando E Del Río Hernández
Tamoxifen has been used for many years to target estrogen receptor signalling in breast cancer cells. Tamoxifen is also an agonist of the G protein-coupled estrogen receptor (GPER), a GPCR ubiquitously expressed in tissues that mediates the acute response to estrogens. Here we report that tamoxifen promotes mechanical quiescence in hepatic stellate cells (HSCs), stromal fibroblast-like cells whose activation triggers and perpetuates liver fibrosis in hepatocellular carcinomas. This mechanical deactivation is mediated by the GPER/RhoA/myosin axis and induces YAP deactivation...
December 21, 2018: Oncogene
https://read.qxmd.com/read/30481931/-yap-regulates-the-proliferation-and-modifies-the-sensitivity-to-sorafenib-in-hepatocellular-carcinoma-cells
#5
L W Guo, G L Shao, J Luo, W Y Hao, Z Yao, J P Zheng
Objective: To detect the expression level of YES-associated protein 1 (YAP) in hepatocellular carcinoma (HCC) cell lines and investigate its effects on the proliferation activity and the sensitivity to sorafenib in HCC cells. Methods: Western blot was used to detect the protein expression levels of YAP in SMMC-7721, SK-Hep-1, HepG-2, Huh7 and the normal liver cell line L-O2. YAP specific small interfering RNA (si-YAP) or YAP expression plasmid were transfected in SK-Hep-1 or Huh7 cells, respectively. Cell counting kit-8 (CCK-8) test was used to detect the cell proliferation activity and the cell cycle test was conducted by flow cytometry...
November 23, 2018: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://read.qxmd.com/read/30410600/huaier-augmented-the-chemotherapeutic-sensitivity-of-oxaliplatin-via-downregulation-of-yap-in-hepatocellular-carcinoma
#6
Yuquan Tao, Liang Shan, Xin Xu, Hongyuan Jiang, Rui Chen, Zijun Qian, Zongguo Yang, Bin Liang, Haiyin Zheng, Feng Cai, Yongchun Yu, Lifang Ma
For unresectable Hepatocellular carcinoma (HCC), chemotherapy is still an important treatment strategy. Oxaliplatin (Oxa) is an effective treatment of HCC after sorafenib treatment failure. However, the intrinsic or acquired resistance of Oxa affected the chemotherapeutic sensitivity. By analyzing the data of GEO Database, we found that Oxa aberrantly increased the expression of Cysteine-rich61 (Cyr61) in HCC cell lines. Subsequently, in Bel-7404 and SMMC-7721 cells after treated with Oxa, it was verified that the expression of Cyr61 and Yes-associated protein (YAP) was increased...
2018: Journal of Cancer
https://read.qxmd.com/read/30405784/emt-induced-by-loss-of-lkb1-promotes-migration-and-invasion-of-liver-cancer-cells-through-zeb1-induced-yap-signaling
#7
Bijun Qiu, Wei Wei, Jianwen Zhu, Guangshun Fu, Dahai Lu
Liver cancer cells often exhibit mesenchymal phenotypes, a critical phenotypic alteration of cancer cells termed the epithelial-mesenchymal transition (EMT). To examine whether liver kinase B1 (LKB1) serves a potential role in EMT in liver carcinogenesis, in the present study, it was determined that the expression of LKB1 decreased in the hepatocellular carcinoma (HCC) cell line, compared with a normal liver cell line. LKB1 overexpression decreased cell motility and invasiveness. Furthermore, the loss of LKB1 induced the expression of several EMT marker proteins, including that of Zinc Finger E-Box Binding Homeobox 1 (ZEB1)...
November 2018: Oncology Letters
https://read.qxmd.com/read/30391347/molecular-evidence-for-better-efficacy-of-hypocrellin-a-and-oleanolic-acid-combination-in-suppression-of-hcc-growth
#8
Lin Wang, Jing Wang, Yuanyuan Cao, Weijie Li, Ying Wang, Jinling Xu, Guanglin Xu
Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancer worldwide and the fifth most common malignancy. The Hippo pathway has been found to play a critical role in cancer development. YAP, a transcriptional coactivator, is the major downstream effector of the Hippo signaling pathway. Hypocrellin A (HA), a natural perylenequinone light-sensitive compound, is usually used for the therapy of eukoplakia of the vulva and keloids in China. Oleanolic acid (OA), a pentacyclic triterpene compound, is prevalent in the treatment of human liver diseases such as viral hepatitis...
November 1, 2018: European Journal of Pharmacology
https://read.qxmd.com/read/30361504/circrna_104075-stimulates-yap-dependent-tumorigenesis-through-the-regulation-of-hnf4a-and-may-serve-as-a-diagnostic-marker-in-hepatocellular-carcinoma
#9
Xiao Zhang, Yanfeng Xu, Zijun Qian, Weisheng Zheng, Qi Wu, Yan Chen, Guoqing Zhu, Ya Liu, Zhixuan Bian, Wen Xu, Yue Zhang, Fenyong Sun, Qiuhui Pan, Jiayi Wang, Lutao Du, Yongchun Yu
Some types of circular RNA (circRNA) are aberrantly expressed in human diseases including hepatocellular carcinoma (HCC). However, its regulation mechanism and diagnostic roles are largely unknown. Here, we identified that circRNA_104075 (circ_104075) was highly expressed in HCC tissues, cell lines and serum. Mechanistically, HNF4a bound to the -1409 to -1401 region of the circ_104075 promoter to stimulate the expression of circ_104075. Moreover, circ_104075 acted as a ceRNA to upregulate YAP expression by absorbing miR-582-3p...
October 25, 2018: Cell Death & Disease
https://read.qxmd.com/read/30340922/interleukin-6-induced-by-yap-in-hepatocellular-carcinoma-cells-recruits-tumor-associated-macrophages
#10
Tian-Yi Zhou, Yu-Lu Zhou, Mei-Jia Qian, Yi-Zheng Fang, Song Ye, Wen-Xiu Xin, Xiao-Chun Yang, Hong-Hai Wu
Tumor-associated macrophages (TAMs) has been regarded as the most prominent component in tumor microenvironment. The correlation between TAM density and poor prognosis in Hepatocellular carcinoma (HCC) patients suggests a supportive role for TAMs in tumor progression. Here we employed a co-culture system to interrogate the molecular link between Yes-Associated Protein (YAP) and TAMs chemotaxis in HCC cells. We found that YAP activation was critical for the recruitment of TAMs towards HCC cells. Furthermore, cytokine array and quantitative RT-PCR analyses showed that IL-6 secreted by YAP-activated HCC cells might induce the TAMs recruitment...
October 2018: Journal of Pharmacological Sciences
https://read.qxmd.com/read/30327349/molecular-profiling-of-nonalcoholic-fatty-liver-disease-associated-hepatocellular-carcinoma-using-sb-transposon-mutagenesis
#11
Takahiro Kodama, Jing Yi, Justin Y Newberg, Jean C Tien, Hao Wu, Milton J Finegold, Michiko Kodama, Zhubo Wei, Takeshi Tamura, Tetsuo Takehara, Randy L Johnson, Nancy A Jenkins, Neal G Copeland
Nonalcoholic fatty liver disease (NAFLD) is the fastest rising cause of hepatocellular carcinoma (HCC) in Western countries; however, the molecular mechanisms that cause NAFLD-HCC remain elusive. To identify molecular drivers of NAFLD-HCC, we performed Sleeping Beauty (SB) transposon mutagenesis screens in liver-specific Pten knockout and in high-fat diet-fed mice, which are murine models of NAFLD-HCC. SB mutagenesis accelerated liver tumor formation in both models and identified 588 and 376 candidate cancer genes (CCGs), respectively; 257 CCGs were common to both screens and were enriched in signaling pathways known to be important for human HCC...
October 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30272278/mir-103-promotes-the-metastasis-and-emt-of-hepatocellular-carcinoma-by-directly-inhibiting-lats2
#12
Li-Li Han, Xiao-Ran Yin, Shu-Qun Zhang
Improving the long‑term survival of patients with hepatocellular carcinoma (HCC) remains a challenge due to metastasis and recurrence. In this study, we demonstrate that the overexpression of miR‑103 in HCC cells promotes epithelial‑mesenchymal transition (EMT), and is associated with an enhanced metastasis and poor outcomes, as shown by western blot analysis and immunohistochemistry. Mechanistically, using reporter luciferase assay we reveal that the serine/threonine‑protein kinase, large tumor suppressor kinase 2 (LATS2), a key component of the Hippo signaling pathway, is a direct target of miR‑103 in HCC cells...
October 1, 2018: International Journal of Oncology
https://read.qxmd.com/read/30251417/decursin-inhibits-the-growth-of-hepg2-hepatocellular-carcinoma-cells-via-hippo-yap-signaling-pathway
#13
Jianchun Li, Honglian Wang, Lu Wang, Ruizhi Tan, Menglian Zhu, Xia Zhong, Yuwei Zhang, Bo Chen, Li Wang
Targeted therapy has a pivotal role for the treatment of liver cancer. The aim of this current study was to examine the effects of decursin on the growth of HepG2 cells and the underlying mechanisms. Our present study showed that treatment of HepG2 cells with decursin significantly inhibited the growth of HepG2 cells by suppressing cell proliferation, cell cycle arresting, and promoting apoptosis in a dose- and time-dependent manner. Most significantly, administration of decursin dramatically impeded in vivo tumor growth in nude mice...
September 24, 2018: Phytotherapy Research: PTR
https://read.qxmd.com/read/30219064/lmo3-promotes-hepatocellular-carcinoma-invasion-metastasis-and-anoikis-inhibition-by-directly-interacting-with-lats1-and-suppressing-hippo-signaling
#14
Yang Cheng, Tianlu Hou, Jian Ping, Tianyang Chen, Baobing Yin
BACKGROUND: In this research, we aimed to investigate the biological functions of LIM domain only 3 (LMO3) in hepatocellular carcinoma (HCC) and uncover the underlying molecular mechanism in it. METHODS: HCC tissue microarray (n = 180) was used to analyze the correlation between LMO3 expression and clinicopathological findings. In vitro transwell matrigel invasion assay and annexin V anoikis assay in HCC cells were conducted to investigate LMO3 related biological functions...
September 15, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/30214243/stard13-is-positively-correlated-with-good-prognosis-and-enhances-5-fu-sensitivity-via-suppressing-cancer-stemness-in-hepatocellular-carcinoma-cells
#15
Fei Gao, Xiaolin Yu, Rongqin Meng, Jisheng Wang, Lin Jia
Background: STARD13 has been revealed to suppress tumor progression. However, the roles in regulating the stemness of hepatocellular carcinoma (HCC) cells are unclear. Methods: Quantitative real-time PCR (qRT-PCR) was used to detect STARD13 expression in HCC tissues and normal adjacent tissues. Kaplan Meier (KM)-plotter analysis was performed to analyze the correlation between STARD13 expression and overall survival of HCC patients. Cell spheroid formation and ALDH1 activity analysis were carried out to detect the effects of STARD13 on the stemness of HCC cells...
2018: OncoTargets and Therapy
https://read.qxmd.com/read/30180863/yes-associated-protein-yap-binds-to-hif-1%C3%AE-and-sustains-hif-1%C3%AE-protein-stability-to-promote-hepatocellular-carcinoma-cell-glycolysis-under-hypoxic-stress
#16
Xiaodong Zhang, Yan Li, Yingbo Ma, Liang Yang, Tao Wang, Xin Meng, Zhihong Zong, Xun Sun, Xiangdong Hua, Hangyu Li
BACKGROUND: Hypoxia-inducible factor 1α (HIF-1α) is essential in hepatocellular carcinoma (HCC) glycolysis and progression. Yes-associated protein (YAP) is a powerful regulator and is overexpressed in many cancers, including HCC. The regulatory mechanism of YAP and HIF-1α in HCC glycolysis is unknown. METHODS: We detected YAP expression in 54 matched HCC tissues and the adjacent noncancerous tissues. The relationship between YAP mRNA expression and that of HIF-1α was analyzed using The Cancer Genome Atlas HCC tissue data...
September 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/30145835/cirrhotic-stiffness-affects-the-migration-of-hepatocellular-carcinoma-cells-and-induces-sorafenib-resistance-through-yap
#17
Jian Gao, Yingxue Rong, Yuxing Huang, Peng Shi, Xitao Wang, Xuan Meng, Jiahong Dong, Congying Wu
A majority of hepatocellular carcinomas (HCCs) combine with liver cirrhosis. The cirrhotic liver has been implicated in interfering with the effects of HCC-targeted drugs, including sorafenib. Alterations in the tumor microenvironment of the cirrhotic liver include both biochemical and biomechanical factors. In this study, we induced sorafenib resistance in HCC cells. We observed changes in cell morphology, cytoskeletal architecture, and cellular stiffness in these sorafenib-resistant cells, resembling those adapted to stiffer substrates...
March 2019: Journal of Cellular Physiology
https://read.qxmd.com/read/30111512/mir-590-5p-suppresses-hepatocellular-carcinoma-chemoresistance-by-targeting-yap1-expression
#18
Minjiang Chen, Liming Wu, Jianfei Tu, Zhongwei Zhao, Xiaoxi Fan, Jianting Mao, Qiaoyou Weng, Xulu Wu, Li Huang, Min Xu, Jiansong Ji
BACKGROUND: Resistance to chemotherapeutic treatment is a common phenomenon in cancers, especially in hepatocellular carcinoma (HCC). The Hippo signaling pathway has been demonstrated to play a role in tumor initiation, development, and progression. However, little is known about its roles in the HCC chemoresistance. METHODS: In this study, real-time PCR and western blotting were used to identify the expression profile of key components of Hippo signaling pathway between chemoresistant and chemosensitive HCC cell lines...
August 13, 2018: EBioMedicine
https://read.qxmd.com/read/30041665/ajuba-inhibits-hepatocellular-carcinoma-cell-growth-via-targeting-of-%C3%AE-catenin-and-yap-signaling-and-is-regulated-by-e3-ligase-hakai-through-neddylation
#19
Min Liu, Ke Jiang, Guibin Lin, Peng Liu, Yumei Yan, Tian Ye, Gang Yao, Martin P Barr, Dapeng Liang, Yang Wang, Peng Gong, Songshu Meng, Haozhe Piao
BACKGROUND: Aberrant activation of β-catenin and Yes-associated protein (YAP) signaling pathways has been associated with hepatocellular carcinoma (HCC) progression. The LIM domain protein Ajuba regulates β-catenin and YAP signaling and is implicated in tumorigenesis. However, roles and mechanism of Ajuba expression in HCC cells remain unclear. The E3 ligase Hakai has been shown to interact with other Ajuba family members and whether Hakai interacts and regulates Ajuba is unknown. METHODS: HCC cell lines stably depleted of Ajuba or Hakai were established using lentiviruses expressing shRNAs against Ajuba or Hakai...
July 24, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/30009820/overexpression-of-rac-gtpase-activating-protein-1-contributes-to-proliferation-of-cancer-cells-by-reducing-hippo-signaling-to-promote-cytokinesis
#20
Xiao-Mei Yang, Xiao-Yan Cao, Ping He, Jun Li, Ming-Xuan Feng, Yan-Li Zhang, Xue-Li Zhang, Ya-Hui Wang, Qin Yang, Lei Zhu, Hui-Zhen Nie, Shu-Heng Jiang, Guang-Ang Tian, Xiao-Xin Zhang, Qiang Liu, Jianguang Ji, Xuefeng Zhu, Qiang Xia, Zhi-Gang Zhang
BACKGROUND & AIMS: Agents designed to block or alter cytokinesis can kill or stop proliferation of cancer cells. We aimed to identify cytokinesis-related proteins that are overexpressed in hepatocellular carcinoma (HCC) cells and might be targeted to slow liver tumor growth. METHODS: Using the Oncomine database, we compared the gene expression patterns in 16 cancer microarray datasets and assessed gene enrichment sets using gene ontology. We performed immunohistochemical analysis of an HCC tissue microarray and identified changes in protein levels that are associated with patient survival times...
October 2018: Gastroenterology
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