scholarly journals Arf6-driven endocytic recycling of CD147 determines HCC malignant phenotypes

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Shanshan Qi ◽  
Linjia Su ◽  
Jing Li ◽  
Chuanshan Zhang ◽  
Zhe Ma ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Membrane Trafficking ◽  
Gelatin Zymography ◽  
Confocal Imaging ◽  
Migration And Invasion ◽  
Endocytic Recycling ◽  
Liver Cancer Cells

Abstract Background Adhesion molecules distributed on the cell-surface depends upon their dynamic trafficking that plays an important role during cancer progression. ADP-ribosylation factor 6 (Arf6) is a master regulator of membrane trafficking. CD147, a tumor-related adhesive protein, can promote the invasion of liver cancer. However, the role of Arf6 in CD147 trafficking and its contribution to liver cancer progression remain unclear. Methods Stable liver cancer cell lines with Arf6 silencing and over-expression were established. Confocal imaging, flow cytometry, biotinylation and endomembrane isolation were used to detect CD147 uptake and recycling. GST-pull down, gelatin zymography, immunofluorescence, cell adhesion, aggregation and tight junction formation, Transwell migration, and invasion assays were used to examine the cellular phenotypes. GEPIA bioinformatics, patient’s specimens and electronic records collection, and immunohistochemistry were performed to obtain the clinical relevance for Arf6-CD147 signaling. Results We found that the endocytic recycling of CD147 in liver cancer cells was controlled by Arf6 through concurrent Rab5 and Rab22 activation. Disruption of Arf6-mediated CD147 trafficking reduced the cell-matrix and cell-cell adhesion, weakened cell aggregation and junction stability, attenuated MMPs secretion and cytoskeleton reorganization, impaired HGF-stimulated Rac1 activation, and markedly decreased the migration and invasion of liver cancer cells. Moreover, high-expression of the Arf6-CD147 signaling components in HCC (hepatocellular carcinoma) was closely correlated with poor clinical outcome of patients. Conclusions Our results revealed that Arf6-mediated CD147 endocytic recycling is required for the malignant phenotypes of liver cancer. The Arf6-driven signaling machinery provides excellent biomarkers or therapeutic targets for the prevention of liver cancer.

scholarly journals Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis

2021 ◽  
Vol 16 (1) ◽  
pp. 1322-1329
Author(s):  
Kebinuer Tuerxun ◽  
Shufang Zhang ◽  
Yuexin Zhang
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Liver Cancer Cell ◽  
Liver Cancer Cells ◽  
And Migration ◽  
Pitx2 Expression

Abstract Paired-like homeodomain 2 (PITX2) functions as a transcription factor to participate in vertebrate embryogenesis, and dysregulated PITX2 expression was associated with the progression of various cancers. The functional role of PITX2 in tumorigenesis of liver cancer remains unknown. Western blot analysis showed that expression levels of PITX2 were enhanced in the liver cancer tissues and cells. siRNAs targeting PITX2 induced downregulation of PITX2 in liver cancer cells. siRNA-induced knockdown of PITX2 decreased liver cancer cell viability and proliferation, while promoting cell apoptosis by increasing cleaved-PARP, cleaved caspase 3, and cleaved caspase 9. The knockdown of PITX2 repressed liver cancer cell migration and invasion. In conclusion, elevated PITX2 expression was associated with liver cancer progression through repression of cell apoptosis and promoting cell proliferation and metastasis, and silencing of PITX2 might serve as a potential therapeutic strategy for the treatment of liver cancer.

scholarly journals The Down-Regulation of SUZ12 Accelerates the Migration and Invasion of Liver Cancer Cells via Activating ERK1/2 Pathway

2019 ◽  
Vol 10 (6) ◽  
pp. 1375-1384 ◽  
Author(s):  
Cailin Xue ◽  
Kunyuan Wang ◽  
Xiaofeng Jiang ◽  
Chengxin Gu ◽  
Ganxiang Yu ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Liver Cancer Cells

scholarly journals Downexpression of HSD17B6 correlates with clinical prognosis and tumor immune infiltrates in hepatocellular carcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lei Lv ◽  
Yujia Zhao ◽  
Qinqin Wei ◽  
Ye Zhao ◽  
Qiyi Yi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Immune Responses ◽  
Cancer Cells ◽  
Negative Regulator ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Relative Reduction ◽  
Clinical Prognosis ◽  
Liver Cancer Cells

Abstract Background Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6), a key protein involved in synthetizing dihydrotestosterone, is abundant in the liver. Previous studies have suggested a role for dihydrotestosterone in modulating progress of various malignancies, and HSD17B6 dysfunction was associated with lung cancer and prostate cancer. However, little is known about the detailed role of HSD17B6 in hepatocellular carcinoma (HCC). Methods Clinical implication and survival data related to HSD17B6 expression in patients with HCC were obtained through TCGA, ICGC, ONCOMINE, GEO and HPA databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The ChIP-seq data were obtained from Cistrome DB. Protein–Protein Interaction and gene functional enrichment analyses were performed in STRING database. The correlations between HSD17B6 and tumor immune infiltrates was investigated via TIMER and xCell. The proliferation, migration and invasion of liver cancer cells transfected with HSD17B6 were evaluated by the CCK8 assay, wound healing test and transwell assay respectively. Expression of HSD17B6, TGFB1 and PD-L1 were assessed by quantitative RT-PCR. Results HSD17B6 expression was lower in HCC compared to normal liver and correlated with tumor stage and grade. Lower expression of HSD17B6 was associated with worse OS, PFS, RFS and DSS in HCC patients. HNF4A bound to enhancer and promoter regions of HSD17B6 gene, activating its transcription, and DNA methylation of HSD17B6 promoter negatively controlled the expression. HSD17B6 and its interaction partners were involved in androgen metabolism and biosynthesis in liver. HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infiltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1. Conclusions This study indicate that HSD17B6 could be a new biomarker for the prognosis of HCC and an important negative regulator of immune responses in HCC.

scholarly journals Roles of CXCL5 on migration and invasion of liver cancer cells

2014 ◽  
Vol 12 (1) ◽  
pp. 193 ◽  
Author(s):  
Xiaojing Xu ◽  
Peixin Huang ◽  
Biwei Yang ◽  
Xiangdong Wang ◽  
Jinglin Xia
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Liver Cancer Cells

scholarly journals miR-18a-5p Targets FBP1 to Promote Proliferation, Migration, and Invasion of Liver Cancer Cells and Inhibit Cell Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Shan Gao ◽  
Dongjie Zhu ◽  
Jian Zhu ◽  
Lianqiang Shen ◽  
Ming Zhu ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Malignant Tumors ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Liver Cancer Cells ◽  
Treatment Plans ◽  
New Treatment

Liver cancer is one of the most aggressive malignant tumors. It is significant to understand the molecular mechanism of liver cancer cells to develop new treatment plans. Studies have identified that FBP1 serves as a cancer inhibitor gene. To research the effect mechanism of FBP1 in liver cancer cells, bioinformatics analysis was performed to study its expression in liver cancer tissue. Survival analysis was also performed. Moreover, starBase database was applied to predict upstream regulatory genes of FBP1. Dual-luciferase assay was performed to testify their targeted relationship. The mRNA and protein expression levels of FBP1 in liver cancer cells were detected by qRT-PCR and western blot, respectively. Cell viability was analyzed by CCK-8 assay. The migratory and invasive abilities of cells were analyzed by Transwell assay. The apoptosis of liver cancer cells was detected by flow cytometry. The results showed that the expression of FBP1 was downregulated in liver cancer tissue and cells. FBP1 low expression was correlated with the poor prognosis of patients. miR-18a-5p could inhibit FBP1 expression. Overexpression of FBP1 could inhibit the progression of liver cancer cells and promote cell apoptosis. Overexpressing miR-18a-5p could promote the progression of liver cancer cells and inhibit cell apoptosis. However, overexpressing FBP1 simultaneously could reverse the effect. miR-18a-5p and FBP1 are expected to be candidates for liver cancer treatment.

scholarly journals Microenvironmental Hypoxia Induces Dynamic Changes in Lung Cancer Synthesis and Secretion of Into Extracellular Vesicles

2020 ◽  
Author(s):  
Shun Wilford Tse ◽  
Chee Fan Tan ◽  
Jung Eun Park ◽  
JebaMercy Gnanasekaran ◽  
Nikhil Gupta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Membrane Trafficking ◽  
Tumour Cell ◽  
Host Immunity ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Functional Clustering

Abstract Background: Extracellular vesicles (EVs) mediate critical intercellular communication within healthy tissues, but are also exploited by tumour cells to promote angiogenesis, metastasis, and host immunosuppression under hypoxic stress. We hypothesize that oxygen starvation in developing tumours induces specific hypoxia-sensitive proteins for packing into small EVs to modulate its microenvironment for cancer progression and enhance malignancy. Methods: We employed a heavy isotope pulse/trace quantitative proteomic approach to study hypoxia-sensitive EVs proteins (HSEPs) in hypoxic A549 lung adenocarcinoma cells derived small EVs (<200 nm). Proteomics data mining and pathway analysis were used to reveal potential roles of the HSEPs in enhancing tumour cell progression and in modulating host immunity. Functional clustering was applied to study enhanced EVs biogenesis and secretion in hypoxic cancer cells. Subsequent biochemical functional assays were performed in A549 and H1299 lung cancer cells to validate the hypoxic cancer-derived EVs in promoting cancer progression.Results: Results revealed that hypoxia stimulated cancer cells to synthesize EVs proteins involved in enhancing tumour cell proliferation (NRSN2, WISP2, SPRX1, LCK), metastasis (GOLM1, STC1, MGAT5B), stemness (STC1, TMEM59), angiogenesis (ANGPTL4), and suppressing host immunity (CD70). In addition, functional clustering analyses revealed that tumour hypoxia was strongly associated with rapid synthesis and EV loading of lysosome-related hydrolases and membrane-trafficking proteins to enhance EVs secretion. Moreover, lung cancer-derived EVs were also enriched in signalling molecules capable of inducing epithelial-mesenchymal transition in recipient cancer cells to promote their migration and invasion. Conclusion: Together, these data indicate that lung cancer-derived EVs can act as paracrine/autocrine mediators of tumorigenesis and metastasis in hypoxic microenvironments. Tumour EVs may therefore offer novel opportunities for useful biomarkers discovery and therapeutic targeting of different cancer types and at different stages according to microenvironmental conditions.

scholarly journals MiR-525-3p Enhances the Migration and Invasion of Liver Cancer Cells by Downregulating ZNF395

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e90867 ◽  
Author(s):  
Fei Pang ◽  
Ruopeng Zha ◽  
Yingjun Zhao ◽  
Qifeng Wang ◽  
Di Chen ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Liver Cancer Cells

scholarly journals Methionine Supplementation Affects Metabolism and Reduces Tumor Aggressiveness in Liver Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2491
Author(s):  
Farida Tripodi ◽  
Beatrice Badone ◽  
Marta Vescovi ◽  
Riccardo Milanesi ◽  
Simona Nonnis ◽  
...  
Keyword(s):  
Cell Growth ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tca Cycle ◽  
Central Carbon Metabolism ◽  
Main Role ◽  
Atp Production ◽  
Liver Cancer Cells ◽  
Methionine Supplementation

Liver cancer is one of the most common cancer worldwide with a high mortality. Methionine is an essential amino acid required for normal development and cell growth, is mainly metabolized in the liver, and its role as an anti-cancer supplement is still controversial. Here, we evaluate the effects of methionine supplementation in liver cancer cells. An integrative proteomic and metabolomic analysis indicates a rewiring of the central carbon metabolism, with an upregulation of the tricarboxylic acid (TCA) cycle and mitochondrial adenosine triphosphate (ATP) production in the presence of high methionine and AMP-activated protein kinase (AMPK) inhibition. Methionine supplementation also reduces growth rate in liver cancer cells and induces the activation of both the AMPK and mTOR pathways. Interestingly, in high methionine concentration, inhibition of AMPK strongly impairs cell growth, cell migration, and colony formation, indicating the main role of AMPK in the control of liver cancer phenotypes. Therefore, regulation of methionine in the diet combined with AMPK inhibition could reduce liver cancer progression.

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