Therapeutic and prognostic importance of epithelial–mesenchymal transition in liver cancers: Insights from experimental models

Ogunwobi, Olorunseun O.; Liu, Chen

doi:10.1016/j.critrevonc.2011.11.007

Cited by 35 publications

(21 citation statements)

References 100 publications

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“…It is well recognized that EMT plays a critical role in HCC cell migration and invasion [37]. Therefore, we explored whether TUSC7 had effects on EMT of HCC.…”

Section: Resultsmentioning

confidence: 99%

Long non-coding RNA TUSC7 acts a molecular sponge for miR-10a and suppresses EMT in hepatocellular carcinoma

et al. 2016

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Despite advances in the roles of long non-coding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) in cancer biology, which has been identified as a tumor suppressor by regulating cell proliferation, apoptosis, migration, invasion, cell cycle, and tumor growth, the function of TUSC7 in hepatocellular carcinoma (HCC) remains unknown. In this study, we observed that the expression of TUSC7 was immensely decreased in HCC. Clinically, the lower expression of TUSC7 predicted poorer survival and may be an independent risk factor for HCC patients. Moreover, TUSC7 inhibited cell metastasis, invasion, and epithelial-to-mesenchymal transformation (EMT) through competitively binding miR-10a. Furthermore, we found that TUSC7 could decrease the expression of Eph tyrosine kinase receptor A4 (EphA4), a downstream target of miR-10a as well as an EMT suppressor, through TUSC7-miR-10a-EphA4 axis. Taken together, we demonstrate that TUSC7 suppresses EMT through the TUSC7-miR-10a-EphA4 axis, which may be a potential target for therapeutic intervention in HCC.

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“…It is well recognized that EMT plays a critical role in HCC cell migration and invasion [37]. Therefore, we explored whether TUSC7 had effects on EMT of HCC.…”

Section: Resultsmentioning

confidence: 99%

Long non-coding RNA TUSC7 acts a molecular sponge for miR-10a and suppresses EMT in hepatocellular carcinoma

et al. 2016

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“…Cancer cells lose their epithelial phenotype and develop a mesenchymal cell phenotype during EMT. EMT further induces the loss of polarity in epithelial cells, reduces cell-cell interactions, and increases cell migration and movement (Yang et al, 2011;Ogunwobi and Liu, 2012). Molecular characteristics of EMT include the downregulation of E-cadherin expression and upregulation of vimentin and fibronectin expression (Yamada et al, 2014;Hou et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Feng¹,

Guo²

2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the expression of T-cell immunoglobulin mucin domain molecule-3 (Tim-3) in osteosarcoma tissues, and analyze its effect on cell proliferation and metastasis in an osteosarcoma cell line. Tim-3 mRNA and protein expression in osteosarcoma tissue was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Additionally, the cell viability, apoptosis rate, and invasive ability of the osteosarcoma cell line MG-63 were tested using the methyl thiazolyl tetrazolium assay, Annexin V-propidium iodide flow cytometry, and a Transwell assay, respectively, following Tim-3 interference using small interfering RNA (siRNA). We also analyzed the expression of Snail, E-cadherin, vimentin, and nuclear factor (NF)-kB in the cells by western blot. We observed that Tim-3 mRNA and protein was significantly overexpressed in osteosarcoma tissues, compared to the adjacent normal tissue (P < 0.01). Moreover, MG-63 cells transfected with the Tim-3 siRNA presented lower cell viability, a greater number of apoptotic cells, and decreased invasive ability (P < 0.01), compared to control cells. Additionally, we observed a decrease in Snail and vimentin expression, an increase in the E-cadherin level, and an increase in NF-kB p65 phosphorylation (P < 0.01) in Tim-3 siRNA-transfected MG-63 cells. Based on these results, we concluded that Tim-3 is highly expressed in osteosarcoma tissue. Moreover, we speculated that interfering in Tim-3 expression could significantly suppress osteosarcoma cell (MG-63) proliferation and metastasis via the NF-kB/Snail signaling pathway and epithelial-mesenchymal transition.

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“…This progression is a function of several phenomena, including (1) epithelial- to-mesenchymal transition (EMT), (2) dissociation of the tumorigenic cells from the host organ (colon) (3) intravasation into vascular circulation and (4) invasion into the 3D environment of the target tissue (liver). 33,47 The cellular pathways and environmental influences linked to these phenomena represent important areas of exploration for understanding metastasis and identifying potential treatment targets. In metastatic colon carcinoma, death is not usually caused by the primary tumor, but by cancer metastases to other organs.…”

Section: Introductionmentioning

confidence: 99%

Liver-Tumor Hybrid Organoids for Modeling Tumor Growth and Drug Response In Vitro

et al. 2015

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Current in vitro models for tumor growth and metastasis are poor facsimiles of in vivo cancer physiology and thus, are not optimal for anti-cancer drug development. Three dimensional (3D) tissue organoid systems, which utilize human cells in a tailored microenvironment, have the potential to recapitulate in vivo conditions and address the drawbacks of current tissue culture dish 2D models. In this study, we created liver-based cell organoids in a rotating wall vessel bioreactor. The organoids were further inoculated with colon carcinoma cells in order to create liver-tumor organoids for in vitro modeling of liver metastasis. Immunofluorescent staining revealed notable phenotypic differences between tumor cells in 2D and inside the organoids. In 2D they displayed an epithelial phenotype, and only after transition to the organoids did the cells present with a mesenchymal phenotype. The cell surface marker expression results suggested that WNT pathway might be involved in the phenotypic changes observed between cells in 2D and organoid conditions, and may lead to changes in cell proliferation. Manipulating the WNT pathway with an agonist and antagonist showed significant changes in sensitivity to the anti-proliferative drug 5-fluoruracil. Collectively, the results show the potential of in vitro 3D liver-tumor organoids to serve as a model for metastasis growth and for testing the response of tumor cells to current and newly discovered drugs.

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Therapeutic and prognostic importance of epithelial–mesenchymal transition in liver cancers: Insights from experimental models

Cited by 35 publications

References 100 publications

Long non-coding RNA TUSC7 acts a molecular sponge for miR-10a and suppresses EMT in hepatocellular carcinoma

Long non-coding RNA TUSC7 acts a molecular sponge for miR-10a and suppresses EMT in hepatocellular carcinoma

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Liver-Tumor Hybrid Organoids for Modeling Tumor Growth and Drug Response In Vitro

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