keyword
https://read.qxmd.com/read/37509410/machine-learning-identifies-a-signature-of-nine-exosomal-rnas-that-predicts-hepatocellular-carcinoma
#21
JOURNAL ARTICLE
Josephine Yu Yan Yap, Laura Shih Hui Goh, Ashley Jun Wei Lim, Samuel S Chong, Lee Jin Lim, Caroline G Lee
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Although alpha fetoprotein (AFP) remains a commonly used serological marker of HCC, the sensitivity and specificity of AFP in detecting HCC is often limited. Exosomal RNA has emerged as a promising diagnostic tool for various cancers, but its use in HCC detection has yet to be fully explored. Here, we employed Machine Learning on 114,602 exosomal RNAs to identify a signature that can predict HCC. The exosomal expression data of 118 HCC patients and 112 healthy individuals were stratified split into Training, Validation and Unseen Test datasets...
July 24, 2023: Cancers
https://read.qxmd.com/read/37414748/diacylglycerol-lipase-alpha-promotes-hepatocellular-carcinoma-progression-and-induces-lenvatinib-resistance-by-enhancing-yap-activity
#22
JOURNAL ARTICLE
Yu-Chuan Yan, Guang-Xiao Meng, Chun-Cheng Yang, Ya-Fei Yang, Si-Yu Tan, Lun-Jie Yan, Zi-Niu Ding, Yun-Long Ma, Zhao-Ru Dong, Tao Li
As an important hydrolytic enzyme that yields 2-AG and free fatty acids, diacylglycerol lipase alpha (DAGLA) is involved in exacerbating malignant phenotypes and cancer progression, but the role of the DAGLA/2-AG axis in HCC progression remains unclear. Here, we found that the upregulation of components of the DAGLA/2-AG axis in HCC samples is correlated with tumour stage and patient prognosis. In vitro and in vivo experiments demonstrated that the DAGLA/2-AG axis promoted HCC progression by regulating cell proliferation, invasion and metastasis...
July 6, 2023: Cell Death & Disease
https://read.qxmd.com/read/37381005/%C3%AE-catenin-interaction-with-yap-foxm1-tead-induced-cep55-supports-liver-cancer-cell-migration
#23
JOURNAL ARTICLE
Yingyue Tang, Lena Thiess, Sofia M E Weiler, Marcell Tóth, Fabian Rose, Sabine Merker, Thomas Ruppert, Peter Schirmacher, Kai Breuhahn
BACKGROUND: Adherens junctions (AJs) facilitate cell-cell contact and contribute to cellular communication as well as signaling under physiological and pathological conditions. Aberrant expression of AJ proteins is frequently observed in human cancers; however, how these factors contribute to tumorigenesis is poorly understood. In addition, for some factors such as α-catenin contradicting data has been described. In this study we aim to decipher how the AJ constituent α-catenin contributes to liver cancer formation...
June 28, 2023: Cell Communication and Signaling: CCS
https://read.qxmd.com/read/37366601/lipophilic-statins-inhibit-yap-co-activator-transcriptional-activity-in-hcc-cells-through-rho-mediated-modulation-of-the-actin-cytoskeleton
#24
JOURNAL ARTICLE
Jihane N Benhammou, Bo Qiao, Arthur Ko, James Sinnett-Smith, Joseph Pisegna, Enrique Rozengurt
<u>Introduction</u>: Hepatocellular carcinoma (HCC) is the third leading cause of liver-related death. Lipophilic statins have been associated with a decrease in HCC incidence, raising the possibility of their use as chemoprevention agents. The Yes associated protein (YAP) and Transcriptional co-Activator (TAZ) have emerged as an important pro-oncogenic mechanism in HCC. Statins modulate YAP/TAZ in other solid tumors but few studies have assessed their mechanisms in HCC. We aimed to delineate how lipophilic statins regulate YAP protein localization by interrogating the mevalonate pathway in a step-wise fashion using pharmacological and genetic approaches in HCC cells...
June 27, 2023: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://read.qxmd.com/read/37312627/nuclear-translocation-of-yap-drives-bmi1-associated-hepatocarcinogenesis-in-hepatitis-b-virus-infection
#25
JOURNAL ARTICLE
Xufeng Luo, Rui Zhang, Stefan Schefczyk, Yaojie Liang, Shu S Lin, Shi Liu, Hideo A Baba, Christian M Lange, Heiner Wedemeyer, Mengji Lu, Ruth Broering
BACKGROUND AND AIMS: Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) development and progression. The aim of this study was to mechanistically investigate the involvement of Hippo signalling in HBV surface antigen (HBsAg)-dependent neoplastic transformation. METHODS: Liver tissue and hepatocytes from HBsAg-transgenic mice were examined for the Hippo cascade and proliferative events. Functional experiments in mouse hepatoma cells included knockdown, overexpression, luciferase reporter assays and chromatin immunoprecipitation...
June 14, 2023: Liver International: Official Journal of the International Association for the Study of the Liver
https://read.qxmd.com/read/37306936/stereotactic-body-radiation-therapy-with-or-without-transarterial-chemoembolization-versus-transarterial-chemoembolization-alone-in-early-stage-hepatocellular-carcinoma-a-systematic-review-and-meta-analysis
#26
REVIEW
Mark P Dumago, Ryan Anthony F Agas, Carl Jay E Jainar, Eugene T Yap, Lester Bryan A Co, Teresa T Sy Ortin
PURPOSE: This study aims to review the current evidence on the utility of stereotactic body radiation therapy (SBRT), with or without transarterial chemoembolization (TACE), for early-stage hepatocellular carcinoma (ESHCC) patients not amenable to standard curative treatment options. METHODS: Literature search was conducted using PubMed, ScienceDirect, and Google Scholar. Comparative studies reporting oncologic outcomes were included in the review. RESULTS: Five studies (one phase II randomized controlled trial, one prospective cohort, three retrospective studies) compared SBRT versus TACE...
December 2023: Journal of Gastrointestinal Cancer
https://read.qxmd.com/read/37243813/activating-the-hippo-pathway-by-nevadensin-overcomes-yap-drived-resistance-to-sorafenib-in-hepatocellular-carcinoma
#27
JOURNAL ARTICLE
Hewen Shi, Ying Zou, Xiaoxue Wang, Guoli Wang, Yijia Gao, Fan Yi, Junqing Xu, Yancun Yin, Defang Li, Minjing Li
BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant type of tumor that is insensitive to cytotoxic chemotherapy and often develops drug resistance. Nevadensin, a bioflavonoid, exhibits anti-cancer properties in some cancers. However, the precise underlying mechanism of nevadensin against liver cancer are poorly understood. We aim to evaluate the efficacy as well as the molecular mechanism of nevadensin in the treatment of liver cancer. METHODS: Effects of nevadensin on HCC cell proliferation and apoptosis were detected using EdU labeling and flow cytometry assays...
May 27, 2023: Discover. Oncology
https://read.qxmd.com/read/37213231/laptm4b-yap-loop-feedback-amplification-enhances-the-stemness-of-hepatocellular-carcinoma
#28
JOURNAL ARTICLE
Jianping Liao, Jiahong Wang, Yu Xu, Yong Wu, Meifeng Wang, Qiudong Zhao, Xiaodan Tan, Yan Meng, Lixin Wei, Aimin Huang
Hepatocellular carcinoma (HCC) is highly heterogeneous, and stemness signatures are frequently elevated in HCC tumor cells to generate heterogeneous subtypes via multidirectional differentiation. However, the mechanisms affecting the regulation of stemness in HCC remain unclear. In this study, we identified that lysosome-associated protein transmembrane-4β (LAPTM4B) was significantly overexpressed in stem-like tumor cell populations with multidirectional differentiation potential at the single cell level, and verified that LAPTM4B was closely related to stemness of HCC using in vitro and in vivo experiments...
June 16, 2023: IScience
https://read.qxmd.com/read/37151879/bulk-and-single-cell-transcriptome-profiling-reveal-extracellular-matrix-mechanical-regulation-of-lipid-metabolism-reprograming-through-yap-tead4-acadl-axis-in-hepatocellular-carcinoma
#29
JOURNAL ARTICLE
Jingwei Cai, Tianyi Chen, Zhiyu Jiang, Jiafei Yan, Zhengtao Ye, Yeling Ruan, Liye Tao, Zefeng Shen, Xiao Liang, Yifan Wang, Junjie Xu, Xiujun Cai
Emerging studies have revealed matrix stiffness promotes hepatocellular carcinoma (HCC) development. We studied metabolic dysregulation in HCC using the TCGA-LIHC database (n=374) and GEO datasets (GSE14520). HCC samples were classified into three heterogeneous metabolic pathway subtypes with different metabolic profiles: Cluster 1, an ECM-producing subtype with upregulated glycan metabolism; Cluster 2, a hybrid subtype with partial pathway dysregulation. Cluster 3, a lipogenic subtype with upregulated lipid metabolism; These three subtypes have different prognosis, clinical features and genomic alterations...
2023: International Journal of Biological Sciences
https://read.qxmd.com/read/37150501/acyl-coa-thioesterase-12-suppresses-yap-mediated-hepatocarcinogenesis-by-limiting-glycerolipid-biosynthesis
#30
JOURNAL ARTICLE
Haiyue He, Akiko Sugiyama, Nathaniel W Snyder, Marcos G Teneche, Xiaowei Liu, Kristal M Maner-Smith, Wolfram Goessling, Susan J Hagen, Eric A Ortlund, S Hani Najafi-Shoushtari, Mariana Acuña, David E Cohen
Cancer cells use acetate to support the higher demand for energy and lipid biosynthesis during uncontrolled cell proliferation, as well as for acetylation of regulatory proteins. Acyl-CoA thioesterase 12 (Acot12) is the enzyme that hydrolyzes acetyl-CoA to acetate in liver cytosol and is downregulated in hepatocellular carcinoma. A mechanistic role for Acot12 in hepatocarcinogenesis was assessed in mice in response to treatment with diethylnitrosamine/carbon tetrachloride administration or prolonged feeding of a diet that promotes non-alcoholic steatohepatitis...
May 5, 2023: Cancer Letters
https://read.qxmd.com/read/37117273/collagen-i-ddr1-signaling-promotes-hepatocellular-carcinoma-cell-stemness-via-hippo-signaling-repression
#31
JOURNAL ARTICLE
Yi-Xiao Xiong, Xiao-Chao Zhang, Jing-Han Zhu, Yu-Xin Zhang, Yong-Long Pan, Yu Wu, Jian-Ping Zhao, Jun-Jie Liu, Yuan-Xiang Lu, Hui-Fang Liang, Zhan-Guo Zhang, Wan-Guang Zhang
Cancer stem cells (CSCs) are a minority population of cancer cells with stemness and multiple differentiation potentials, leading to cancer progression and therapeutic resistance. However, the concrete mechanism of CSCs in hepatocellular carcinoma (HCC) remains obscure. We found that in advanced HCC tissues, collagen I was upregulated, which is consistent with the expression of its receptor DDR1. Accordingly, high collagen I levels accompanied by high DDR1 expression are associated with poor prognoses in patients with HCC...
July 2023: Cell Death and Differentiation
https://read.qxmd.com/read/37085881/fgfr4-and-ezh2-inhibitors-synergistically-induce-hepatocellular-carcinoma-apoptosis-via-repressing-yap-signaling
#32
JOURNAL ARTICLE
Yiqi Yang, Yibo Zhang, Jieqiong Cao, Zijian Su, Fu Li, Peiguang Zhang, Bihui Zhang, Rongzhan Liu, Linhao Zhang, Junye Xie, Jingsheng Li, Jinting Zhang, Xiaojia Chen, An Hong
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide, but current treatment options remain limited and cause serious life-threatening side effects. Aberrant FGFR4 signaling has been validated as an oncogenic driver of HCC, and EZH2, the catalytic subunit of the PRC2 complex, is a potential factor that contributes to acquired drug resistance in many tumors, including HCC. However, the functional relationship between these two carcinogenic factors, especially their significance for HCC treatment, remains unclear...
April 22, 2023: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/37041150/usp1-modulates-hepatocellular-carcinoma-progression-via-the-hippo-taz-axis
#33
JOURNAL ARTICLE
Dongyi Liu, Quanhui Li, Yifeng Zang, Xin Li, Zhongbo Li, Peng Zhang, Chang Feng, Penghe Yang, Jiayao Cui, Yanan Sun, Tian Wei, Peng Su, Xin Zhao, Huijie Yang, Yinlu Ding
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. The Hippo signaling pathway has emerged as a significant suppressive pathway for hepatocellular carcinogenesis. The core components of the Hippo pathway constitute a kinase cascade, which inhibits the functional activation of YAP/TAZ. Interestingly, the overactivation of YAP/TAZ is commonly observed in hepatocellular carcinoma, although the inhibitory kinase cascade of the Hippo pathway is still functional. Recent studies have indicated that the ubiquitin‒proteasome system also plays important roles in modulating Hippo signaling activity...
April 12, 2023: Cell Death & Disease
https://read.qxmd.com/read/36920600/hepatitis-c-virus-nonstructural-protein-4b-induces-lipogenesis-via-the-hippo-pathway
#34
JOURNAL ARTICLE
Chen Zou, Hongxi Tan, Jun Zeng, Minqi Liu, Guangping Zhang, Yi Zheng, Zhanfeng Zhang
Hepatitis C virus (HCV) infection causes abnormal lipid metabolism in hepatocytes, which leads to hepatic steatosis and even hepatocellular carcinoma. HCV nonstructural protein 4B (NS4B) has been reported to induce lipogenesis, but the underlying mechanism is unclear. In this study, western blots were performed to investigate the effect of NS4B protein levels on key effectors of the Hippo and AKT signaling pathways. Yes-associated protein (YAP) and moesin-ezrin-radixin-like protein (Merlin) are effectors of the Hippo pathway...
March 15, 2023: Archives of Virology
https://read.qxmd.com/read/36920042/akr1c3-suppresses-ferroptosis-in-hepatocellular-carcinoma-through-regulation-of-yap-slc7a11-signaling-pathway
#35
JOURNAL ARTICLE
Jinsi Chen, Jia Zhang, Wei Tian, Chao Ge, Yuting Su, Jinjun Li, Hua Tian
AKR1C3 is frequently overexpressed and it is a validated therapeutic target in various tumors including hepatocellular carcinoma (HCC). Our previous study showed that AKR1C3 facilitated HCC proliferation and metastasis by forming a positive feedback loop of AKR1C3-NF-κB-STAT3. Ferroptosis is a form of iron-dependent cell death driven by iron-dependent accumulation of lipid reactive oxygen species and plays an important role in tumor suppression. However, little is known about the role of AKR1C3 in ferroptosis susceptibility...
March 15, 2023: Molecular Carcinogenesis
https://read.qxmd.com/read/36919851/two-hippo-signaling-modules-orchestrate-liver-size-and-tumorigenesis
#36
JOURNAL ARTICLE
Sixian Qi, Zhenxing Zhong, Yuwen Zhu, Yebin Wang, Mingyue Ma, Yu Wang, Xincheng Liu, Ruxin Jin, Zhihan Jiao, Rui Zhu, Zhao Sha, Kyvan Dang, Ying Liu, Dae-Sik Lim, Junhao Mao, Lei Zhang, Fa-Xing Yu
The Hippo pathway is a central regulator of organ size and tumorigenesis and is commonly depicted as a kinase cascade, with an increasing number of regulatory and adaptor proteins linked to its regulation over recent years. Here, we propose that two Hippo signaling modules, MST1/2-SAV1-WWC1-3 (HPO1) and MAP4K1-7-NF2 (HPO2), together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators. In mouse livers, the genetic inactivation of either HPO1 or HPO2 module results in partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC)...
March 15, 2023: EMBO Journal
https://read.qxmd.com/read/36918225/society-for-immunotherapy-of-cancer-sitc-consensus-definitions-for-resistance-to-combinations-of-immune-checkpoint-inhibitors-with-targeted-therapies
#37
JOURNAL ARTICLE
Michael B Atkins, Paolo A Ascierto, David Feltquate, James L Gulley, Douglas B Johnson, Nikhil I Khushalani, Jeffrey Sosman, Timonthy A Yap, Harriet Kluger, Ryan J Sullivan, Hussein Tawbi
Immunotherapy offers deep and durable disease control to some patients, but many tumors do not respond to treatment with single-agent immune checkpoint inhibitors (ICIs). One strategy to enhance responses to immunotherapy is via combinations with signal transduction inhibitors, such as antiangiogenic therapies, which not only directly target cancer cells but also could potentially favorably modulate the tumor immune microenvironment. Combination strategies with ICIs have demonstrated enhanced antitumor activity compared with tumor-targeted or antiangiogenic therapy alone in randomized trials in a variety of solid tumor settings, leading to regulatory approval from the US Food and Drug Administration and agencies in other countries for the treatment of endometrial cancer, kidney cancer, melanoma, and hepatocellular carcinoma...
March 2023: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/36894036/a-therapeutically-targetable-taz-tead2-pathway-drives-the-growth-of-hepatocellular-carcinoma-via-anln-and-kif23
#38
JOURNAL ARTICLE
Yoshinobu Saito, Dingzi Yin, Naoto Kubota, Xiaobo Wang, Aveline Filliol, Helen Remotti, Ajay Nair, Ladan Fazlollahi, Yujin Hoshida, Ira Tabas, Kirk J Wangensteen, Robert F Schwabe
BACKGROUND & AIMS: Despite recent progress, long-term survival remains low for hepatocellular carcinoma (HCC). The most effective HCC therapies target the tumor immune microenvironment (TIME), and there are almost no therapies that directly target tumor cells. Here, we investigated the regulation and function of tumor cell-expressed Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in HCC. METHODS: HCC was induced in mice by Sleeping Beauty-mediated expression of MET, CTNNB1-S45Y, or TAZ-S89A, or by diethylnitrosamine plus CCl4 ...
June 2023: Gastroenterology
https://read.qxmd.com/read/36824917/the-essential-role-of-o-glcnacylation-in-hepatic-differentiation
#39
Dakota R Robarts, Manasi Kotulkar, Diego Paine-Cabrera, Kaitlyn K Venneman, John A Hanover, Natasha E Zachara, Chad Slawson, Udayan Apte
BACKGROUND & AIMS: O-GlcNAcylation is a post-translational modification catalyzed by the enzyme O-GlcNAc transferase (OGT), which transfers a single N-acetylglucosamine sugar from UDP-GlcNAc to the protein on serine and threonine residues on proteins. Another enzyme, O-GlcNAcase (OGA), removes this modification. O-GlcNAcylation plays an important role in pathophysiology. Here, we report that O-GlcNAcylation is essential for hepatocyte differentiation, and chronic loss results in fibrosis and hepatocellular carcinoma...
February 17, 2023: bioRxiv
https://read.qxmd.com/read/36806855/tea-domain-transcriptional-factor-4-tead4-mitigates-tgf-%C3%AE-signaling-and-hepatocellular-carcinoma-progression-independently-of-yap
#40
JOURNAL ARTICLE
Weicheng Luo, Yi Li, Yi Zeng, Yining Li, Minzhang Cheng, Cheng Zhang, Fei Li, Yiqing Wu, Chunhong Huang, Xiaolong Yang, Joachim Kremerskothen, Jianmin Zhang, Chunbo Zhang, Shuo Tu, Zhihua Li, Zhijun Luo, Zhenghong Lin, Xiaohua Yan
Tea domain transcriptional factor 4 (TEAD4) plays a pivotal role in tissue development and homeostasis by interacting with YAP in response to Hippo signaling inactivation. TEAD4 and YAP can also cooperate with TGF-β-activated Smad proteins to regulate gene transcription. Yet, it remains unclear whether TEAD4 might play a YAP-independent role in TGF-β signaling. Here, we unveil a novel tumor suppressive function of TEAD4 in liver cancer via mitigation of TGF-β signaling. Ectopic TEAD4 inhibited TGF-β-induced signal transduction, Smads transcriptional activity, and their target gene transcription, consequently suppressing hepatocellular carcinoma (HCC) cell proliferation and migration in vitro and xenograft tumor growth in mice...
February 20, 2023: Journal of Molecular Cell Biology
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