Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines

Avci, M. Ender; Keşküş, Ayşe Gökçe; Targen, Seniye; Işılak, Musa Efe; Öztürk, Mehmet; Cetin-Atalay, Rengül; Adams, Michelle M.; Konu, Özlen

doi:10.1038/s41598-018-19817-w

Cited by 30 publications

(26 citation statements)

References 63 publications

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“…Statistical methods included Analysis of variance (ANOVA), Student's t-test and linear regression. Zebrafish xenograft data was statistically analyzed with chi-square with Yates correction as described in previous study [34]. Results with p < 0.05 were considered as statistically significant.…”

Section: Discussionmentioning

confidence: 99%

lncRNA HOTAIR overexpression induced downregulation of c-Met signaling promotes hybrid epithelial/mesenchymal phenotype in hepatocellular carcinoma cells

et al. 2020

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Background: Epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) are both reversible processes, and regulation of phenotypical transition is very important for progression of several cancers including hepatocellular carcinoma (HCC). Recently, it is defined that cancer cells can attain a hybrid epithelial/ mesenchymal (hybrid E/M) phenotype. Cells with hybrid E/M phenotype comprise mixed epithelial and mesenchymal properties, they can be more resistant to therapeutics and also more capable of initiating metastatic lesions. However, the mechanisms regulating hybrid E/M in HCC are not well described yet. In this study, we investigated the role of the potential crosstalk between lncRNA HOTAIR and c-Met receptor tyrosine kinase, which are two essential regulators of EMT and MET, in acquiring of hybrid E/M phenotype in HCC. Methods: Expression of c-Met and lncRNA HOTAIR were defined in HCC cell lines and patient tissues through HCC progression. lncRNA HOTAIR was overexpressed in SNU-449 cells and its effects on c-Met signaling were analyzed. c-Met was overexpressed in SNU-398 cells and its effect on HOTAIR expression was analyzed. Biological significance of HOTAIR/c-Met interplay was defined in means of adhesion, proliferation, motility behavior, invasion, spheroid formation and metastatic ability. Effect of ectopic lncRNA HOTAIR expression on phenotype was defined with investigation of molecular epithelial and mesenchymal traits. Results: In vitro and in vivo experiments verified the pivotal role of lncRNA HOTAIR in acquisition of hybrid E/M phenotype through modulating expression and activation of c-Met and its membrane co-localizing partner Caveolin-1, and membrane organization to cope with the rate limiting steps of metastasis such as survival in adhesion independent microenvironment, escaping from anoikis and resisting to fluidic shear stress (FSS) in HCC. Conclusions: Our work provides the first evidence suggesting a role for lncRNA HOTAIR in the modulation of c-Met to promote hybrid E/M phenotype. The balance between lncRNA HOTAIR and c-Met might be critical for cell fate decision and metastatic potential of HCC cells.

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Section: Discussionmentioning

confidence: 99%

lncRNA HOTAIR overexpression induced downregulation of c-Met signaling promotes hybrid epithelial/mesenchymal phenotype in hepatocellular carcinoma cells

et al. 2020

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“…Primary antibodies are described in Immunofluorescent analysis of the cells HCC cells were grown on glass cover-slips and after experimental conditions set, cells were immunofluorescently labeled as described in previous study (27). statistically analyzed with chi-square with Yates correction as described in previous study (32).…”

Section: Immunoblottingmentioning

confidence: 99%

lncRNA HOTAIR overexpression promotes hybrid epithelial/mesenchymal phenotype through suppression of c-Met Receptor Tyrosine Kinase Signaling in Hepatocellular Carcinoma Cells

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et al. 2020

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Background: Epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) are both reversible processes, and regulation of phenotypical transition is very important for progression of several cancers including hepatocellular carcinoma (HCC). Recently, it is defined that cancer cells can attain a hybrid epithelial/mesenchymal (hybrid E/M) phenotype. Cells with hybrid E/M phenotype comprise mixed epithelial and mesenchymal properties, they can be more resistant to therapeutics and also more capable of initiating metastatic lesions. However, the mechanisms regulating hybrid E/M in HCC are not well described yet. In this study, we investigated the role of the potential crosstalk between lncRNA HOTAIR and c-Met receptor tyrosine kinase, which are two essential regulators of EMT and MET, in acquiring of hybrid E/M phenotype in HCC.Methods: Expression of c-Met and HOTAIR were defined in HCC cell lines and patient tissues through HCC progression. lncRNA HOTAIR was overexpressed in SNU-449 cells and its effects on c-Met signaling were analyzed. c-Met was overexpressed in SNU-398 cells and its effect on HOTAIR expression was analyzed. Biological significance of HOTAIR/c-Met interplay was defined in means of adhesion, proliferation, motility behavior, invasion, spheroid formation and metastatic ability. Effect of ectopic HOTAIR expression on phenotype was defined with investigation of molecular epithelial and mesenchymal traits.Results: In vitro and in vivo experiments verified the pivotal role of lncRNA HOTAIR in acquisition of hybrid E/M phenotype through modulating c-Met and its membrane co-localizing partner Caveolin-1 expression, activation and membrane organization to cope with the rate limiting steps of metastasis such as survival in adhesion independent microenvironment, escaping from anoikis and resisting to fluidic shear stress (FSS) in HCC.Conclusions: Our work provides the first evidence suggesting a role for lncRNA HOTAIR in the modulation of c-Met to promote hybrid E/M phenotype. The balance between lncRNA HOTAIR and c-Met might be critical for cell fate decision and metastatic potential of HCC cells.

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“…Acetylcholine (ACh) is involved in a variety of cell biological behaviors, such as cell proliferation, cell differentiation, cell migration and cellular immune response, so the accumulation of ACh in the tumor microenvironment directly or indirectly supports tumor growth [ 41 ]. Acetylcholinesterase (AChE) plays key role in the cholinergic system, and its dysregulation is involved in a variety of human diseases [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

Protein liposomes-mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy

et al. 2021

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Background Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy. Results Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. Conclusions This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.

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Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines

Cited by 30 publications

References 63 publications

lncRNA HOTAIR overexpression induced downregulation of c-Met signaling promotes hybrid epithelial/mesenchymal phenotype in hepatocellular carcinoma cells

lncRNA HOTAIR overexpression induced downregulation of c-Met signaling promotes hybrid epithelial/mesenchymal phenotype in hepatocellular carcinoma cells

lncRNA HOTAIR overexpression promotes hybrid epithelial/mesenchymal phenotype through suppression of c-Met Receptor Tyrosine Kinase Signaling in Hepatocellular Carcinoma Cells

Protein liposomes-mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy

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