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HCC signaling pathway

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https://www.readbyqxmd.com/read/28637000/precision-medicine-for-hepatocellular-carcinoma-driver-mutations-and-targeted-therapy
#1
REVIEW
Xiao-Xiao Ding, Qing-Ge Zhu, Shi-Ming Zhang, Lei Guan, Ting Li, Lei Zhang, Shi-Yang Wang, Wan-Li Ren, Xue-Mei Chen, Jing Zhao, Song Lin, Zhi-Zhen Liu, Yan-Xia Bai, Bing He, Hu-Qin Zhang
Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called "driver mutations". The discovery of driver mutations provides a novel precision medicine strategy for late stage HCC, called targeted therapy...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636424/fluid-shear-stress-regulates-hepg2-cell-migration-though-time-dependent-integrin-signaling-cascade
#2
Hongchi Yu, Yang Shen, Jingsi Jin, Yingying Zhang, Tang Feng, Xiaoheng Liu
Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear...
June 21, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28634059/a-pumpkin-polysaccharide-induces-apoptosis-by-inhibiting-the-jak2-stat3-pathway-in-human-hepatoma-hepg2-cells
#3
Weixi Shen, Chunhong Chen, Yuanyuan Guan, Xiaowei Song, Yinghua Jin, Jingfang Wang, Yu Hu, Tao Xin, Qiuying Jiang, Li Zhong
The purpose of this study is to investigate the effect of a purified polysaccharide (PPPF) from pumpkin fruit on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. The results showed that PPPF or STAT3 siRNA inhibits the cell growth of HepG2 cells via induction of apoptosis. Moreover, PPPF is able to suppress both constitutive and IL-6-induced phosphorylation of STAT3 (on Tyr705) and subsequent nuclear translocation in cancer cells. Such inhibition is found to be achieved through down-regulation of constitutive phosphorylation of JAK2, but not JAk1, c-Src, ERK1/2, and Akt, which means STAT3 tyrosine phosphorylation in HepG2 cells following PPPF treatment is associated with a reduction in JAK2 activity...
June 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28628795/knockout-of-the-nogo-b-gene-attenuates-tumor-growth-and-metastasis-in-hepatocellular-carcinoma
#4
Bo Zhu, Shaobo Chen, Xiaoding Hu, Xiaofeng Jin, Yichen Le, Lihuan Cao, Zhonghua Yuan, Zhen Lin, Songmin Jiang, Lichun Sun, Long Yu
Human hepatocellular carcinoma (HCC) is a malignant cancer. It is a challenge to develop anti-HCC drugs due to HCC's extreme aggressiveness and with the sensitivity of the liver to show severe adverse effects. More importantly, the precise mechanisms causing HCC pathogenicity are not known. Our previous study disclosed Nogo-B as a reticulon 4 (Rtn4) family member. In the present study, we first identified that Nogo-B played a critical role in HCC progression. We found, via in vitro and in vivo assays, that Nogo-B was expressed aberrantly in primary HCC tumor tissues and immortal HCC cells but was relatively scarce in the normal liver tissues or cells...
June 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28627705/targeting-the-pd-l1-dnmt1-axis-in-acquired-resistance-to-sorafenib-in-human-hepatocellular-carcinoma
#5
Jianhua Liu, Yahui Liu, Lingyu Meng, Kai Liu, Bai Ji
Molecule-targeted therapy, such as sorafenib, is one of the effectively therapeutic options for advanced hepatocellular carcinoma (HCC). However, acquired resistance to sorafenib has been found in some HCC patients, resulting in poor prognosis. It is reported that PD-L1 and DNA methyltransferases (DNMTs) contribute to drug resistance. In this study, by inducing sorafenib-resistant HCC cell lines, we investigated their molecular and functional characteristics. Our data indicated that highly upregulated DNMT1 was positively correlated with PD-L1 overexpression in sorafenib-resistant HCC cells...
June 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627623/p18-peptide-a-functional-fragment-of-pigment-epithelial-derived-factor-inhibits-angiogenesis-in-hepatocellular-carcinoma-via-modulating-vegf-vegfr2-signalling-pathway
#6
Xin Wang, Peng Xiu, Fuhai Wang, Jingtao Zhong, Honglong Wei, Zongzhen Xu, Feng Liu, Jie Li
The P18 peptide is a functional fragment of pigment epithelial-derived factor (PEDF), which is an endogenic angiogenesis inhibitor. This study sought to determine the anti-angiogenic bioactivity of the P18 peptide in hepato-cellular carcinoma (HCC) and to elucidate the underlying mechanism. Xenograft tumour growth assays demonstrated the P18 peptide suppressed angiogenesis of HCC in vivo. Wound healing, Transwell and Matrigel-culture assays indicated that the P18 peptide inhibited the cell migration and tube formation of endothelial cells (ECs) in vitro...
June 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28624790/co-targeting-of-igf1r-mtor-pathway-by-mir-497-and-mir-99a-impairs-hepatocellular-carcinoma-development
#7
Henghui Cheng, Jin Xue, Shouhua Yang, Yaobin Chen, Yu Wang, Yuanli Zhu, Xiaoyan Wang, Dong Kuang, Qiurong Ruan, Yaqi Duan, Guoping Wang
Persistent activation of IGF1R/mTOR signaling pathway plays crucial role in the development of hepatocellular carcinoma (HCC). Therefore, our goal was to elucidate microRNAs (miRNAs) targeting IGF1R/mTOR and the therapeutic potential of single or dual miRNA on HCC development. In this study, we found that miR-497 and miR-99a that target the 3'-UTR of both IGF1R and mTOR were down-regulated in HCC human tissues and cell lines. Functional assay revealed that ectopic expression of miR-497 or miR-99a in HCC cells resulted in a significant inhibition on tumor growth and invasiveness in vitro and tumor development in vivo via repressing the expression of IGF1R and mTOR...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624623/mitochondrial-fission-forms-a-positive-feedback-loop-with-cytosolic-calcium-signaling-pathway-to-promote-autophagy-in-hepatocellular-carcinoma-cells
#8
Qichao Huang, Haiyan Cao, Lei Zhan, Xiacheng Sun, Gang Wang, Jibin Li, Xu Guo, Tingting Ren, Zhe Wang, Yinghua Lyu, Bingrong Liu, Jiaze An, Jinliang Xing
Both mitochondrial morphology and the level of cytosolic calcium [Ca(2+)]c are actively changed and play critical roles in a number of malignancies. However, whether communications existed between these two processes to ingeniously control the malignant phenotype are far from clear. We investigated the reciprocal regulation between mitochondrial fission and cytosolic calcium signaling in human hepatocellular carcinoma (HCC) cells. Furthermore, the underlying molecular mechanisms and the synergistic effect on autophagy were explored...
June 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28622593/long-noncoding-rna-linc00462-promotes-hepatocellular-carcinoma-progression
#9
JianDe Gong, XuFei Qi, Yi Zhang, YingCong Yu, XiZhou Lin, HongLiang Li, YiRen Hu
BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most common malignancies worldwide. In two pubic long noncoding RNA (lncRNA) profiling studies of HCC, linc00462 was consistently upregulated. We analyzed the clinical significance and biological role of linc00462 in HCC. METHODS: We performed quantitative real-time PCR analysis to determine the levels of linc00462 in HCC tissues from 49 patients. Functional analysis was performed in cell lines and in an animal model to support clinical findings...
June 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28619606/pivotal-roles-of-glycogen-synthase-3-in-hepatocellular-carcinoma
#10
REVIEW
Melchiorre Cervello, Giuseppa Augello, Antonella Cusimano, Maria Rita Emma, Daniele Balasus, Antonina Azzolina, James A McCubrey, Giuseppe Montalto
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, and represents the second most frequently cancer and third most common cause of death from cancer worldwide. At advanced stage, HCC is a highly aggressive tumor with a poor prognosis and with very limited response to common therapies. Therefore, there is still the need for new effective and well-tolerated therapeutic strategies. Molecular-targeted therapies hold promise for HCC treatment. One promising molecular target is the multifunctional serine/threonine kinase glycogen synthase kinase 3 (GSK-3)...
June 6, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28619511/aqp5-promotes-hepatocellular-carcinoma-metastasis-via-nf-%C3%AE%C2%BAb-regulated-epithelial-mesenchymal-transition
#11
Zhikuan He, Wenxing Dong, Junhong Hu, Xuequn Ren
Aquaporin 5 (AQP5), a transmembrane protein, is known for its involvement in the progress of many diseases such as chronic kidney disease and systemic disease. Recently, AQP5 has been reported to play an important role in cancer progression. However, little is known about its precise functions in hepatocellular carcinoma (HCC). This study aimed to investigate the specific role of AQP5 in HCC. The results showed that AQP5 was highly expressed in HCC cell lines and its down-regulation inhibited HCC cell invasion and tumor metastasis in vitro and in vivo...
June 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28616586/the-autotaxin-lysophosphatidic-acid-pathway-emerges-as-a-therapeutic-target-to-prevent-liver-cancer
#12
Derek J Erstad, Andrew M Tager, Yujin Hoshida, Bryan C Fuchs
Using transcriptome meta-analysis, we recently identified the autotaxin (ATX)-lysophosphatidic acid (LPA) pathway as a regulator of hepatocellular carcinoma (HCC) risk in human cirrhosis patients. Pharmacological targeting of this pathway reduced fibrosis progression and HCC development in animals, identifying ATX-LPA signaling as a novel chemoprevention strategy for cirrhosis and HCC.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28607595/e2f8-is-a-potential-therapeutic-target-for-hepatocellular-carcinoma
#13
REVIEW
Yi Lv, Jia Xiao, Jing Liu, Feiyue Xing
E2F transcriptional factors are widely expressed in a number of tissues and organs, possessing many regulatory functions related to cellular proliferation, differentiation, DNA repair, cell-cycle and cell apoptosis. E2F8 is a recently identified member of the E2F family with a duplicated DNA-binding domain feature discriminated from E2F1-6, controlling gene expression in a dimerization partner-independent manner. It is indispensable for angiogenesis, lymphangiogenesis and embryonic development. Although E2F8 and E2F7 perform complementary and overlapping functions in many cell metabolisms, E2F8, but not E2F7, overexpresses remarkably in hepatocellular carcinoma (HCC) to facilitate the HCC occurrence and development via activating a E2F1/ Cyclin D1 signaling pathway to regulate the G1- to S-phase transition of cell cycle progression or transcriptionally suppressing CDK1 to induce hepatocyte polyploidization...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28605041/calcium-binding-protein-39-promotes-hepatocellular-carcinoma-growth-and-metastasis-by-activating-erk-signaling-pathway
#14
Lingxi Jiang, Qian Yan, Shuo Fang, Ming Liu, Li Yan, Yun-Fei Yuan, Yan Li, Yinghui Zhu, Jiali Qi, Xiaodong Yang, Dora Lai Wan Kwong, Xin-Yuan Guan
Calcium binding protein (CAB39) is a key regulator of a group of STE20 kinases. Here we report that CAB39 was frequently up-regulated in hepatocellular carcinoma (HCC), which was significantly associated with tumor metastasis (P=0.000), poorer disease-free survival rate (P=0.027) and poor prognosis (P=0.000). Ectopic expression of CAB39 in immortalized human liver cell line LO2 and HCC cell lines QGY-7703 and BEL-7402 could increase foci formation, colony formation in soft agar, tumor formation in nude mice and cell motility...
June 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28604762/tip30-regulates-lipid-metabolism-in-hepatocellular-carcinoma-by-regulating-srebp1-through-the-akt-mtor-signaling-pathway
#15
F Yin, G Sharen, F Yuan, Y Peng, R Chen, X Zhou, H Wei, B Li, W Jing, J Zhao
Lipid reprogramming has been considered as a crucial characteristic in hepatocellular carcinoma (HCC) initiation and progression. However, detailed molecular mechanisms have yet to be clearly defined. Here, we examined the effects of tumor suppressor TIP30 on the regulation of HCC lipid metabolism. We found that decreased TIP30 expression leads to elevated fatty acid synthesis and enhanced levels of lipogenic enzymes SCD and FASN in HCC cells. Moreover, SREBP1 is one of the key transcription factors regulating liver lipid metabolism, and TIP30 deficiency significantly increased SREBP1 expression and nuclear accumulation...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28604110/emerging-tyrosine-kinase-inhibitors-for-the-treatment-of-hepatocellular-carcinoma
#16
Laure de Rosamel, Jean-Frederic Blanc
Hepatocellular carcinoma (HCC) is the fifth most diagnosed cancer in the world and the third leading cause of death. Unfortunately, when diagnosed two thirds of patients have an advanced disease for which only palliative treatment can be proposed and most likely systemic therapy. Areas covered: As of today only one systemic therapy is validated in the treatment of advanced HCC, a tyrosine kinase inhibitor (TKI): Sorafenib. Treatment options are therefore lacking. With the advent of Sorafenib other TKIs have been studied with some disappointing results...
June 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28600143/involvement-of-pi3k-akt-pathway-in-the-inhibition-of-hepatocarcinoma-cell-invasion-and-metastasis-induced-by-sash1-through-downregulating-shh-gli1-signaling
#17
Changyu Sun, Zhihao Zhang, Ping He, Yan Zhou, Xuhua Xie
The SASH1 gene is discovered as a tumor suppressor recently. However, the molecular mechanisms of SASH1 in hepatocarcinoma (HCC) remain unclear. In present studies, we investigated the molecular mechanisms of SASH1 on cell invasion and metastasis of hepatocarcinoma in vivo and in vitro. In this study, SASH1 overexpression HCC cell lines were treated with purmorphamine (0, 0.5, 1, 2μmol/l). Western blot and qRT-PCR were used to examine the related gene expression of EMT markers and the Shh-Gli1 and PI3K/Akt-dependent pathway...
June 7, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28599479/dynamin-3-suppresses-growth-and-induces-apoptosis-of-hepatocellular-carcinoma-cells-by-activating-inducible-nitric-oxide-synthase-production
#18
Chao Gu, Junliang Yao, Peilong Sun
Dynamin 3 (DNM3) is candidate tumor suppressor against hepatocellular carcinoma (HCC). Downregulation of DNM3 is more frequently identified in HCC tissues than in normal liver tissues. However, the mechanism underlying DNM3-mediated inhibition of HCC remains unclear. The present study demonstrated that DNM3 expression was decreased in human HCC tissues and cell lines. The downregulation of DNM3 promoted cell proliferation by increasing cell cycle-associated proteins, including cyclin D1, cyclin-dependent kinase (CDK) 2 and CDK4...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28598821/overexpression-of-centromere-protein-k-cenp-k-gene-in-hepatocellular-carcinoma-promote-cell-proliferation-by-activating-akt-tp53-signal-pathway
#19
Haiyan Wang, Weilong Liu, Lei Liu, Chi Wu, Weigang Wu, Juan Zheng, Mingxia Zhang, Xinchun Chen, Boping Zhou, Zhiliang Gao, Jian Huang
Hepatocellular carcinoma (HCC) is one of the high-incidence malignant tumors with very poor prognosis. Identification of potential oncogenes is critical to discovering novel therapeutic targets for many cancers, including HCC. In our previous studies, using microarray technology, we conformed that CENP-K was overexpressed in HCCs. However, whether the overexpression of CENP-K contributes to hepatocarcinogenesis remains unclear. In this study, we found that CENP-K was significantly up-regulated in 60% (63 of 105) of HCC specimens at the mRNA level compared to adjacent non-cancerous liver specimens, as determined by RT-qPCR...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591730/downregulation-of-serum-rab27b-confers-improved-prognosis-and-is-associated-with-hepatocellular-carcinoma-progression-through-pi3k-akt-p21-signaling
#20
Xue Yang, Xieqiong Ye, Le Sun, Fangyuan Gao, Yuxin Li, Xiaomin Ji, Xuejiang Wang, Ying Feng, Xianbo Wang
Previous study revealed that elevated expression of RAB27B in tissues is correlated with hepatocellular carcinoma (HCC) progression; however, the mechanisms involved in promoting HCC development are still unclear. Moreover, HCC tissues are not readily obtained during routine diagnosis. Therefore, to further explore its potential value in early diagnosis, we examined RAB27B expression in patient sera. First, the correlation between serum RAB27B expression and survival, as well as TNM and Barcelona Clinic Liver Cancer stages, were evaluated in patients with HCC...
May 19, 2017: Oncotarget
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