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catenin hepatocellular carcinoma

Guangyu Yu, Wenshuang Wang, Junfeng Deng, Shaohua Dong
The oncogenic role of the long noncoding RNA associated with poor prognosis of hepatocellular carcinoma (lncRNA AWPPH) was reported in various types of malignancies; however, its involvement in ovarian carcinoma (OC) remains unknown. Thus, the present study investigated the role of AWPPH in OC. The expression of AWPPH in tissues and serum acquired from patients with OC, and healthy controls, was determined via reverse transcription‑quantitative polymerase chain reaction. The diagnostic value of serum AWPPH expression was evaluated by receiver operating characteristic curve analysis...
March 14, 2019: Molecular Medicine Reports
Saad Saffo, Tamar H Taddei
Hepatocellular carcinoma (HCC) arises from a number of cirrhosis-related and non-cirrhosis-related exposures and is one of the leading causes of cancer-related deaths worldwide. Achieving a durable cure currently relies on either resection or transplantation, but since most patients will be diagnosed with inoperable disease, there is great interest in achieving more effective systemic therapies. At a molecular level, HCC is heterogeneous, but initial treatment strategies, including the use of multi-targeted tyrosine kinase inhibitors and checkpoint inhibitors, have been fairly homogenous, depending on general host factors and overall tumor burden rather than specific molecular signatures...
March 18, 2019: Digestive Diseases and Sciences
Xiaoling Luo, Yuting Liu, Shijie Ma, Lei Liu, Rui Xie, Shaochuang Wang
BACKGROUND: Wnt ligand binding initiates the interaction between Frizzled and Dvl proteins. However, the regulation of Frizzled-Dvl proteins interaction remains largely unknown. AIMS: The present study aims to elucidate the regulation of Frizzled-Dvl interaction by WDR34. METHODS: The protein levels of WDR34 in hepatocellular carcinoma (HCC) tissues were examined by western blot and immunohistochemistry. The effects of WDR34 on the growth and migration of HCC cells were examined using MTT assay and Boyden chamber assay...
March 15, 2019: Digestive Diseases and Sciences
Atsushi Takai, Hien Dang, Naoki Oishi, Subreen Khatib, Sean P Martin, Dana A Dominguez, Ji Luo, Rachel Bagni, Xiaolin Wu, Katie Powell, Qing-Hai Ye, Huliang Jia, Lun-Xiu Qin, Jinqiu Chen, Gary Alexander Mitchell, Xiaoling Luo, Snorri S Thorgeirsson, Xin W Wang
Hepatocellular carcinoma (HCC) is a genetically heterogeneous disease for which a dominant actionable molecular driver has not been identified. Patients with the stem cell-like EpCAM+AFP+ HCC subtype have poor prognosis. Here we performed a genome-wide RNAi screen to identify genes with a synthetic lethal interaction with EpCAM as a potential therapeutic target for the EpCAM+AFP+ HCC subtype. We identified 26 candidate genes linked to EpCAM/Wnt/β-catenin signaling and HCC cell growth. We further characterized the top candidate PMPCB, which plays a role in mitochondrial protein processing, as a bona fide target for EpCAM+ HCC...
March 12, 2019: Cancer Research
Hao Yang, Rongxuan Zhu, Xiaoping Zhao, Liu Liu, Zhaoli Zhou, Li Zhao, Beibei Liang, Wenjing Ma, Jian Zhao, Jianjun Liu, Gang Huang
Tumor cells undergo a metabolic shift in order to adapt to the altered microenvironment, although the underlying mechanisms have not been fully explored. HnRNP A1 is involved in the alternative splicing of the pyruvate kinase (PK) mRNA, allowing tumor cells to specifically produce the PKM2 isoform. We found that the acetylation status of hnRNP A1 in hepatocellular carcinoma (HCC) cells was dependent on glucose availability, which affected the PKM2-dependent glycolytic pathway. In the glucose-starved HCC cells, SIRT1 and SIRT6, members of deacetylase sirtuin family, were highly expressed and deacetylated hnRNP A1 after direct binding...
March 11, 2019: Oncogene
Zhongyi Fan, Jingjing Duan, Lingxiong Wang, Saisong Xiao, Lingling Li, Xiang Yan, Wei Yao, Liangliang Wu, Sujie Zhang, Yong Zhang, Ye Li, Xiang Zhu, Yi Hu, Dong Zhang, Shunchang Jiao, Xiaojie Xu
Emerging evidence indicates that cancer stem cells (CSCs) are involved in tumorigenesis, tumor recurrence, and therapeutic resistance in hepatocellular carcinoma (HCC). However, the mechanisms underlying HCC CSC regulation remain largely unknown. Here we report our analysis of 97 paraffin-embedded HCC tumor specimens. We found that protein tyrosine kinase 2 (PTK2) expression correlated with liver CSC marker expression, overall survival, and recurrence-free survival in HCC patients. Our results further showed that PTK2 activated Wnt/β-catenin signaling by promoting nuclear accumulation of β-catenin in HCC cells...
March 5, 2019: Cancer Letters
Yongxu Chen, Huihong Wen, Cheng Zhou, Qiao Su, Yongxin Lin, Yingjie Xie, Yajing Huang, Qixuan Qiu, Juze Lin, Xuhui Huang, Wei Tan, Cunyun Min, Changjun Wang
M2-polarized tumor-associated macrophages (M2-TAMs) infiltrating the tumor microenvironment contribute to hepatocellular carcinoma (HCC) progression. It was reported that cancer cells undergoing EMT will acquire stemness characteristics. Here, the HCC SMMC-7721 cell line was co-cultured with M2-TAMs polarized from THP-1 cells in vitro. In in vivo studies, we used nude mice subcutaneous tumor model to test whether the growth of the tumor was affected by M2-TAMs. Subsequently, EMT, stemness and Wnt/β-catenin pathway related markers were detected in cells and subcutaneous tumor tissues...
March 4, 2019: Experimental Cell Research
Xiangxian Xu, Dazhi Gao, Xiaoli Yuan, L I Liu, Xiang Zhang, Xianxian Liang, Sui Chen, Min Ai, B O Chen, Donghong Shi, Zhijian Yang, Robert M Hoffman, Jian Xu
BACKGROUND/AIM: Transcatheter arterial chemoembolization (TACE) is one of the most widely used palliative therapies for the unresectable hepatocellular carcinoma (HCC). However, a large difference is found in prognosis among patients treated with TACE. The aim of the present study was to investigate the prognostic value of β-catenin in HCC patients treated with TACE. MATERIALS AND METHODS: Seventy patients with HCC were included in this study. Expression of β-catenin was determined by immunohistochemistry in biopsy samples taken before TACE...
March 2019: Anticancer Research
A S Arboatti, F Lambertucci, M G Sedlmeier, G Pisani, J Monti, M de L Álvarez, D E A Francés, M T Ronco, C E Carnovale
Obesity has been implicated in the genesis of metabolic syndromes including insulin resistance and Type 2 Diabetes Mellitus (T2DM). Given the association between T2DM and the risk of hepatocellular carcinoma (HCC), our specific goal was to determine whether the liver of HFD-induced T2DM mice is more sensitive to the carcinogen diethylnitrosamine (DEN), due to a modification of the molecular pathways implicated in the early stages of HCC pathogenesis. C57BL/6 male mice (five-week-old) were divided into 4 groups: C, C + DEN, HFD and HFD + DEN...
February 28, 2019: Chemico-biological Interactions
Ning Zhang, Hui Li, Chengdong Qin, Dening Ma, Yiming Zhao, Weiping Zhu, Lu Wang
PURPOSE: Radiofrequency ablation (RFA) therapy has proven to be effective and feasible for early-stage hepatocellular carcinoma (HCC); however, rapid progression of residual tumor cells after RFA has been confirmed, but the molecular mechanisms of this phenomenon are poorly understood. This study evaluated the effect of the lipid raft proteins known as flotillins on the invasive and metastatic potential of residual HCC. METHODS: The human HCC cell line HCCLM3 was used to establish insufficient RFA models in vivo and in vitro...
February 28, 2019: Journal of Cancer Research and Clinical Oncology
Siwen Dang, Jingshi Zhou, Yijun Chen, Pu Chen, Meiju Ji, Bingyin Shi, Qi Yang, Peng Hou
Hepatitis B virus (HBV) infection is the primary cause of hepatocellular carcinoma (HCC). Zinc-finger protein 382 (ZNF382), which belongs to zinc-finger protein family, has been documented to be downregulated in certain types of cancer. However, its role in HCC remains largely unknown. In this study, we demonstrated that ZNF382 expression was significantly elevated in HBV-infected liver cirrhosis tissues relative to HBV-negative normal liver tissues at protein levels, but not at mRNA levels, and was positively correlated with the levels of HBV DNA and hepatitis B virus X protein (HBx)...
February 25, 2019: Oncogene
Lilia Turcios, Eduardo Chacon, Catherine Garcia, Pedro Eman, Virgilius Cornea, Jieyun Jiang, Brett Spear, Chunming Liu, David S Watt, Francesc Marti, Roberto Gedaly
Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/β-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells...
2019: PloS One
Lulu Xie, Hanhan Dai, Minjing Li, Wei Yang, Guohua Yu, Xia Wang, Peiyuan Wang, Wei Liu, Xuemei Hu, Mingdong Zhao
Membrane-associated RING-CH-1 (MARCH1) is a membrane-anchored E3 ubiquitin ligase that is involved in a variety of cellular processes. MARCH1 was aberrantly expressed as a tumour promoter in ovarian cancer, but the signalling about the molecular mechanism has not yet been fully illuminated. Here, we first determined that MARCH1 was obviously highly expressed in human hepatocellular carcinoma samples and cells. In addition, our findings demonstrated that the proliferation, migration and invasion of hepatocellular carcinoma were suppressed, but the apoptosis was increased, as a result of MARCH1 knockdown by either siRNA targeting MARCH1 or pirarubicin treatment...
February 22, 2019: Journal of Cellular and Molecular Medicine
Hong Gao, Fen-Fen Yin, Dong-Xian Guan, Yu-Xiong Feng, Qian-Wen Zheng, Xiang Wang, Min Zhu, Xue-Li Zhang, Shu-Qun Cheng, Tian-Wei Chen, Hao Jiang, Er-Bin Zhang, Jing-Jing Wang, Qian-Zhi Ni, Yan-Mei Yuan, Feng-Kun Zhang, Ning Ma, Hui-Jun Cao, Yi-Kang Wang, Jing-Jing Li, Dong Xie
OBJECTIVES: Wnt1-inducible signalling pathway protein 3 (WISP3/CCN6) belongs to the CCN (CYR61/CTGF/NOV) family of proteins, dysregulation of this family contributed to the tumorigenicity of various tumours. In this study, we need to explore its role in hepatocellular carcinoma that remains largely elusive. MATERIALS AND METHODS: The expression of WISP3/CCN6 was analysed by qRT-PCR and Western blotting. Effects of WISP3 on proliferation and metastasis of HCC cells were examined, respectively, by MTT assay and Boyden Chamber...
February 22, 2019: Cell Proliferation
Hung Huynh, Richard Ong, Kah Yong Goh, Liek Yeow Lee, Florian Puehler, Arne Scholz, Oliver Politz, Dominik Mumberg, Karl Ziegelbauer
Mutations affecting the Wnt/β‑catenin pathway have been identified in 26‑40% of hepatocellular carcinoma (HCC) cases. Aberrant activation of this pathway leads to uncontrolled cell proliferation and survival. Thus, identifying Wnt/β‑catenin pathway inhibitors may benefit a subset of patients with HCC. In the present study, the effects of sorafenib and a MEK inhibitor on tumor growth and Wnt/β‑catenin signaling in HCC models were evaluated. A β‑catenin mutant and β‑catenin wild‑type HCC models were treated once daily with i) 10 mg/kg sorafenib, ii) 15 mg/kg refametinib (or 25 mg/kg selumetinib), or iii) sorafenib/refametinib...
January 23, 2019: International Journal of Oncology
Yu Qiao, Jingxiao Wang, Eylul Karagoz, Binyong Liang, Xinhua Song, Runze Shang, Katja Evert, Meng Xu, Li Che, Matthias Evert, Diego F Calvisi, Junyan Tao, Bruce Wang, Satdarshan P Monga, Xin Chen
Inactivating mutations of AXIN1, a negative regulator of the Wnt/β-Catenin cascade, are among the common genetic events in human hepatocellular carcinoma (HCC), affecting around 10% of cases. In the present manuscript, we sought to define the genetic crosstalk between Axin1 mutants and Wnt/β-catenin as well as Notch signaling cascades along hepatocarcinogenesis. We discovered that c-MET activation and AXIN1 mutations occur concomitantly in ~3 to 5% of human HCC samples. Subsequently, we generated a murine HCC model via CRISPR/Cas9 based gene deletion of Axin1 (sgAxin1) in combination with transposon-based expression of c-Met in the mouse liver (c-Met/sgAxin1)...
February 8, 2019: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Chiara Sartor, Laura Bachelot, Cécile Godard, Franck Lager, Gilles Renault, Frank J Gonzalez, Christine Perret, Angélique Gougelet, Sabine Colnot
BACKGROUND/AIMS: Loss of hepatocyte nuclear factor-4α (HNF4α), a critical factor driving liver development and differentiation, is frequently associated with hepatocellular carcinoma (HCC). Our recent data revealed that HNF4α level was decreased in mouse and human HCCs with activated β-catenin signaling. In addition, increasing HNF4α level by miR-34a inhibition slowed tumor progression of β-catenin activated HCC in mice. METHODS: We generated a Hnf4aflox/flox/ Apcflox/flox /TTR-CreERT 2 (Hnf4a/Apc∆Hep ) mouse line and evaluated the impact of Hnf4a disruption on HCC development and liver homeostasis...
February 5, 2019: Liver International: Official Journal of the International Association for the Study of the Liver
Ji-Hua Shi, Wen-Zhi Guo, Yang Jin, Hua-Peng Zhang, Chun Pang, Jie Li, Pål-Dag Line, Shui-Jun Zhang
BACKGROUND: The ERBB2 oncogene hypothesis is challenged in hepatocellular carcinoma (HCC) with the conflicting evidences of human epidermal growth factor receptor 2 (HER2) overexpression. HER2 could be a new target as a treatment option for HCC as well as tumor recurrence after surgery. HER2 in HCC biology needs further explorations. METHODS: Clinical and mRNA data of HCC patients were obtained from TCGA HCC cohort, GSE89377 and GSE115018. Western Blotting and immunohistochemistry were employed to test expression of HER2, E-cadherin, and Vimentin...
February 4, 2019: Cancer Medicine
Adeola O Adebayo Michael, Sungjin Ko, Junyan Tao, Akshata Moghe, Hong Yang, Meng Xu, Jacquelyn O Russell, Tirthadipa Pradhan-Sundd, Silvia Liu, Sucha Singh, Minakshi Poddar, Jayvir S Monga, Pin Liu, Michael Oertel, Sarangarajan Ranganathan, Aatur Singhi, Sandra Rebouissou, Jessica Zucman-Rossi, Silvia Ribback, Diego Calvisi, Natalia Qvartskhava, Boris Görg, Dieter Häussinger, Xin Chen, Satdarshan P Monga
Based on their lobule location, hepatocytes display differential gene expression, including pericentral hepatocytes that surround the central vein, which are marked by Wnt-β-catenin signaling. Activating β-catenin mutations occur in a variety of liver tumors, including hepatocellular carcinoma (HCC), but no specific therapies are available to treat these tumor subsets. Here, we identify a positive relationship between β-catenin activation, its transcriptional target glutamine synthetase (GS), and p-mTOR-S2448, an indicator of mTORC1 activation...
January 28, 2019: Cell Metabolism
Wanhu Fan, Fenjing Du, Xiaojing Liu
Tripartite motif 66 (TRIM66) protein, a member of the tripartite motif (TRIM) protein superfamily, has emerged as an oncogenic protein that is closely related to carcinogenesis in multiple cancers. However, whether TRIM66 plays a role in the progression of hepatocellular carcinoma (HCC) remains unknown. This study was aimed to investigate TRIM66 expression and its potential biological function in HCC cell lines. Here we showed that TRIM66 expression was significantly upregulated in HCC cell lines compared with normal control cells...
January 30, 2019: European Journal of Pharmacology
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