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HCC signaling pathway

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https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#1
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445189/stk17b-promotes-carcinogenesis-and-metastasis-via-akt-gsk-3%C3%AE-snail-signaling-in-hepatocellular-carcinoma
#2
Yaliang Lan, Jihua Han, Yan Wang, Jiabei Wang, Guangchao Yang, Keyu Li, Ruipeng Song, Tongsen Zheng, Yingjian Liang, Shangha Pan, Xirui Liu, Mingxi Zhu, Yao Liu, Fanzheng Meng, Manzoor Mohsin, Yifeng Cui, Bo Zhang, Sharma Subash, Lianxin Liu
Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide with frequent intrahepatic and distant metastasis. Elucidating the underlying molecular mechanism that modulates HCC progression is critical for exploring novel therapeutic strategies. Serine/Threonine Kinase 17B (STK17B) is upregulated in HCC tissues, but its role in HCC progression remains elusive. In the present studies, we reported that STK17B had a critical role in HCC progression. STK17B was significantly upregulated in HCC cell lines and specimens, and patients with ectopic STK17B expression characterized with poor clinicopathological features...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445139/dynamic-network-biomarker-indicates-pulmonary-metastasis-at-the-tipping-point-of-hepatocellular-carcinoma
#3
Biwei Yang, Meiyi Li, Wenqing Tang, Weixin Liu, Si Zhang, Luonan Chen, Jinglin Xia
Developing predictive biomarkers that can detect the tipping point before metastasis of hepatocellular carcinoma (HCC), is critical to prevent further irreversible deterioration. To discover such early-warning signals or biomarkers of pulmonary metastasis in HCC, we analyse time-series gene expression data in spontaneous pulmonary metastasis mice HCCLM3-RFP model with our dynamic network biomarker (DNB) method, and identify CALML3 as a core DNB member. All experimental results of gain-of-function and loss-of-function studies show that CALML3 could indicate metastasis initiation and act as a suppressor of metastasis...
February 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29445127/cripto-1-contributes-to-stemness-in-hepatocellular-carcinoma-by-stabilizing-dishevelled-3-and-activating-wnt-%C3%AE-catenin-pathway
#4
Regina Cheuk-Lam Lo, Carmen Oi-Ning Leung, Kristy Kwan-Shuen Chan, Daniel Wai-Hung Ho, Chun-Ming Wong, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Identification and characterization of functional molecular targets conferring stemness properties in hepatocellular carcinoma (HCC) offers crucial insights to overcome the major hurdles of tumor recurrence, metastasis and chemoresistance in clinical management. In the current study, we investigated the significance of Cripto-1 in contributing to HCC stemness. Cripto-1 was upregulated in the sorafenib-resistant clones derived from HCC cell lines and patient-derived xenograft that we previously developed, suggesting an association between Cripto-1 and stemness...
February 14, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29445087/rage-induces-hepatocellular-carcinoma-proliferation-and-sorafenib-resistance-by-modulating-autophagy
#5
Jun Li, Peng-Wen Wu, Yuan Zhou, Bo Dai, Peng-Fei Zhang, Yu-Hen Zhang, Yang Liu, Xiao-Lei Shi
The receptor for advanced glycation end products (Rage) is involved in the development of various tumors and acts as an oncogenic protein. Rage is overexpressed in tumors including hepatocellular carcinoma (HCC). However, the molecular mechanism of Rage in HCC progression and sorafenib resistance remains unclear. In this study, enhanced Rage expression is highly associated proliferation and contributes to sorafenib resistance. Rage deficiency contributed to autophagy induction through activating AMPK/mTOR signaling pathway, which is important for sorafenib response...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29443924/identification-of-key-pathways-and-genes-in-the-dynamic-progression-of-hcc-based-on-wgcna
#6
Li Yin, Zhihui Cai, Baoan Zhu, Cunshuan Xu
Hepatocellular carcinoma (HCC) is a devastating disease worldwide. Though many efforts have been made to elucidate the process of HCC, its molecular mechanisms of development remain elusive due to its complexity. To explore the stepwise carcinogenic process from pre-neoplastic lesions to the end stage of HCC, we employed weighted gene co-expression network analysis (WGCNA) which has been proved to be an effective method in many diseases to detect co-expressed modules and hub genes using eight pathological stages including normal, cirrhosis without HCC, cirrhosis, low-grade dysplastic, high-grade dysplastic, very early and early, advanced HCC and very advanced HCC...
February 14, 2018: Genes
https://www.readbyqxmd.com/read/29442042/trim59-promotes-cell-proliferation-migration-and-invasion-in-human-hepatocellular-carcinoma-cells
#7
Gang Sun, Xin Sui, Dayue Han, Jianjun Gao, Yining Liu, Lin Zhou
The human tripartite motif (TRIM) 59 has been implicated in tumorigenesis of many types of cancer. However, the biological function and molecular mechanism of TRIM59 in hepatocellular carcinoma (HCC) remains unknown. In our study, the purpose was to investigate the impact of TRIM59 on the biologic behavior of HCC cells. We observed that TRIM59 was highly expressed in HCC cells compared with a normal human hepatocyte cell line. Lentivirus-mediated knocking down of TRIM59 significantly suppressed the proliferation, migration and invasion of HCC cells, whereas overexpression of TRIM59 enhanced cell growth and metastasis...
November 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29441724/prmt5-promotes-cell-proliferation-by-inhibiting-btg2-expression-via-the-erk-signaling-pathway-in-hepatocellular-carcinoma
#8
Hai Jiang, Yue Zhu, Zhenyu Zhou, Junyang Xu, Shaowen Jin, Kang Xu, Heyun Zhang, Qing Sun, Jie Wang, Junyao Xu
Increasing evidence suggests that PRMT5, a protein arginine methyltransferase, has roles in cell growth regulation and cancer development. However, the role of PRMT5 in hepatocellular carcinoma (HCC) progression remains unclear. Here, we showed that PRMT5 expression was frequently upregulated in HCC tissues, and its expression was inversely correlated with overall survival in HCC patients. PRMT5 knockdown markedly inhibited in vitro HCC proliferation and in vivo tumorigenesis. We revealed that the mechanism of PRMT5-induced proliferation was partially mediated by BTG downregulation, leading to cell cycle arrest during the G1 phase in HCC cells...
February 14, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29440144/spon2-promotes-m1-like-macrophage-recruitment-and-inhibits-hepatocellular-carcinoma-metastasis-by-distinct-integrin-rho-gtpase-hippo-pathways
#9
Yan-Li Zhang, Qing Li, Xiao-Mei Yang, Fang Fang, Jun Li, Ya-Hui Wang, Qin Yang, Lei Zhu, Hui-Zhen Nie, Xue-Li Zhang, Ming-Xuan Feng, Shu-Heng Jiang, Guang-Ang Tian, Li-Peng Hu, Ho-Young Lee, Su-Jae Lee, Qiang Xia, Zhi-Gang Zhang
Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis...
February 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/29439719/myl6b-a-myosin-light-chain-promotes-mdm2-mediated-p53-degradation-and-drives-hcc-development
#10
Xingwang Xie, Xueyan Wang, Weijia Liao, Ran Fei, Nan Wu, Xu Cong, Qian Chen, Lai Wei, Yu Wang, Hongsong Chen
BACKGROUND: Identification of novel MDM2 or p53 binding proteins may reveal undefined oncogenes, tumor suppressors, signaling pathways and possible treatment targets. METHODS: By means of immunoprecipitation and Mass Spectrometry analysis, we aimed to identify novel regulators of the MDM2-p53 pathway. We further clarified the impact of MYL6B on the p53 protein level and on the process of apoptosis. We also investigated the role of MYL6B in hepatocellular carcinoma by clone formation assay and by determining the correlation between its expression and prognosis of HCC patients...
February 13, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29439259/downregulation-of-prame-suppresses-proliferation-and-promotes-apoptosis-in-hepatocellular-carcinoma-through-the-activation-of-p53-mediated-pathway
#11
Hanzhang Zhu, Jingrui Wang, Junjie Yin, Bei Lu, Qijun Yang, Yafeng Wan, Changku Jia
BACKGROUND/AIMS: The expression of PRAME and its role in hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to examine the functional role of PRAME in HCC development and exploring the molecular mechanism. METHODS: We first detected PRAME expression in 96 human HCC tissue samples and correlated with clinicopathological characteristics and prognosis of the patients. We then established stable HCC cell lines with PRAME overexpression and knockdown followed by functional analysis in vitro...
February 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29439255/co-upregulation-of-14-3-3%C3%AE-and-p-akt-is-associated-with-oncogenesis-and-recurrence-of-hepatocellular-carcinoma
#12
Yufu Tang, Ruoyu Wang, Yibing Zhang, Shenhui Lin, Na Qiao, Zhongyi Sun, Shuqun Cheng, Wenping Zhou
BACKGROUND/AIMS: 14-3-3ζ is involved in the regulation of PI3K/Akt pathway which is closely associated with carcinogenesis. However, the clinical significance of combined detection of 14-3-3ζ and p-Akt in hepatocellular carcinoma (HCC) remains unclear. METHODS: Two-hundred pairs of HCC and adjacent liver specimens were subjected to tissue microarray. The association of 14-3-3ζ and p-Akt levels with the postoperative survival and recurrence in HCC patients was analyzed with univariate and multivariate methods...
February 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29438745/an-automated-epifluorescence-microscopy-imaging-assay-for-the-identification-of-phospho-akt-level-modulators-in-breast-cancer-cells
#13
Elke Kaemmerer, Dane Turner, Amelia A Peters, Sarah J Roberts-Thomson, Gregory R Monteith
AKT is an enzyme of the PI3K/pAKT pathway, regulating proliferation and cell survival. High basal levels of active, phosphorylated AKT (pAKT) are associated with tumor progression and therapeutic resistance in some breast cancer subtypes, including HER2 positive breast cancers. Various stimuli can increase pAKT levels and elevated basal pAKT levels are a feature of PTEN-deficient breast cancer cell lines. The aim of this study was to develop an assay able to identify modulators of pAKT levels using an automated epifluorescence microscope and high content analysis...
February 10, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29436633/microarray-analysis-for-the-identification-of-specific-proteins-and-functional-modules-involved-in-the-process-of-hepatocellular-carcinoma-originating-from-cirrhotic-liver
#14
Wufeng Fan, Guangming Ye
In order to identify the potential pathogenesis of hepatocellular carcinoma (HCC) developing from cirrhosis, a microarray‑based transcriptome profile was analyzed. The GSE63898 expression profile was downloaded from the Gene Expression Omnibus database, which included data from 228 HCC tissue samples and 168 cirrhotic tissue samples. The Robust Multi‑array Average in the Affy package of R was used for raw data processing and Student's t‑test was used to screen differentially expressed genes (DEGs). An enrichment analysis was then conducted using the Database for Annotation, Visualization and Integrated Discovery online tool, and the protein‑protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape...
February 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29434983/analysis-of-expression-profile-data-identifies-key-genes-and-pathways-in-hepatocellular-carcinoma
#15
Xuwei Jiang, Yuqing Hao
The aims of the present study were to identify key genes and pathways associated with hepatocellular carcinoma (HCC) progression and predict compounds potentially associated with this type of carcinogenesis. The gene expression profile data of the GSE49515 dataset was obtained from the Gene Expression Omnibus database. The limma software package was used to identify the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Biological Networks Gene Ontology tool and the Database for Annotation, Visualization and Integrated Discovery, respectively...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434911/novel-betulin-derivative-induces-anti-proliferative-activity-by-g2-m-phase-cell-cycle-arrest-and-apoptosis-in-huh7-cells
#16
Zhen-Jian Zhuo, Min-Jie Xiao, Hui-Ran Lin, Jing Luo, Tao Wang
Betulin (BT) has been identified to exhibit potential benefits for treating hepatocellular carcinoma (HCC). The results of the present study demonstrated that a new semisynthetic derivative of BT, 3,28-di-(2-nitroxy-acetyl)-oxy-BT, may effectively decrease the viability of Huh7 cells. Mechanistic studies revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT inhibited the transition between G2 and M phase of the cell cycle by regulating cell cycle regulatory proteins. Additional study revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT may trigger Huh7 cells to undergo caspase-dependent apoptosis as an increased proportion of cells were identified in the sub-G1 phase, which may be a result of poly(ADP-ribose) polymerase cleavage and caspase activation...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434780/berbamine-induces-smmc-7721-cell-apoptosis-via-upregulating-p53-downregulating-survivin-expression-and-activating-mitochondria-signaling-pathway
#17
Ying Cao, Jianbo Cao, Binbin Yu, Shusheng Wang, Lili Liu, Li Tao, Wanping Sun
Hepatocellular carcinoma (HCC) is a primary malignancy in the liver, which is a global health problem. The present study aimed to observe the apoptotic effects of berbamine on SMMC-7721 cell lines and to investigate the effects of berbamine on induction of the intrinsic apoptotic pathway. The human HCC SMMC-7721 cells were cultured and cell morphology observed using a phase contrast microscope. SMMC-7721 cell apoptosis was examined by employing a flow cytometry assay. The nuclei of SMMC-7721 cells were stained with DAPI and observed by utilizing a laser fluorescence microscope...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434703/microrna-495-suppresses-cell-proliferation-and-invasion-of-hepatocellular-carcinoma-by-directly-targeting-insulin-like-growth-factor-receptor-1
#18
Ying Ye, Juhua Zhuang, Guangdong Wang, Saifei He, Suiliang Zhang, Guoyu Wang, Jing Ni, Jiening Wang, Wei Xia
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and second-most frequent cause of cancer-associated deaths worldwide. Previously, increasing studies report that microRNAs (miRNAs/miRs) are abnormally expressed in various types of human cancers and may participate in the tumourigenesis and tumour development of HCC. miRNA-based targeted therapy is effective against different molecular targets and may increase the sensitisation of cancer cells to therapy by several folds. Therefore, further validation of potentially important miRNAs involved in HCC initiation and progression may provide valuable insights into the treatment of patients with HCC...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29432845/adam9-mediates-the-interleukin-6-induced-epithelial-mesenchymal-transition-and-metastasis-through-ros-production-in-hepatoma-cells
#19
Yinying Dong, Zhifeng Wu, Mingyan He, Yuhan Chen, Yixing Chen, Xiaoyun Shen, Xiaomei Zhao, Li Zhang, Baoying Yuan, Zhaochong Zeng
Interleukin (IL)-6 has been implicated in the invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular events that mediate this process are poorly understood. Here, we showed that IL-6 promoted the epithelial-mesenchymal transition (EMT) in HCC cell lines, and upregulated a disintegrin and metalloprotease 9 (ADAM9) expression by activating the JNK signaling pathway. ADAM9 was upregulated in human HCCs which promoted HCC cell invasion and the EMT by interacting with NADPH oxidase 1 and inducing reactive oxygen species generation...
February 9, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29431199/n-glycosylation-by-n-acetylglucosaminyltransferase-v-enhances-the-interaction-of-cd147-basigin-with-integrin-%C3%AE-1-and-promotes-hcc-metastasis
#20
Jian Cui, Wan Huang, Bo Wu, Jin Jin, Lin Jing, Wen-Pu Shi, Zhen-Yu Liu, Lin Yuan, Dan Luo, Ling Li, Zhi-Nan Chen, Jian-Li Jiang
While the importance of protein N-glycosylation in cancer cell migration is well appreciated, the precise mechanisms by which N-acetylglucosaminyltransferase V (GnT-V) regulates cancer processes remain largely unknown. In the current study, we report that GnT-V mediated N-glycosylation of CD147/Basigin, a tumor-associated glycoprotein that carries β1,6 N-acetylglucosamine (β1,6 GlcNAc) glycans, is upregulated during TGF-β1-induced epithelial-to-mesenchymal transition (EMT), which correlates with tumor metastasis in patients with hepatocellular carcinoma (HCC)...
February 12, 2018: Journal of Pathology
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