Coexpression of Vimentin and Keratins by Human Melanoma Tumor Cells: Correlation With Invasive and Metastatic Potential

Hendrix, Mary J.C.; Seftor, Elisabeth A.; Chu, Yi; Seftor, Richard E.B.; Nagle, Raymond B.; Mcdaniel, Kathleen M.; Leong, Stanley P. L.; Yohem, K. H.; Leibovitz, Albert; Meyskens, Frank L.; Conaway, Dale H.; Welch, Danny R.; Liotta, Lance A.; Stetler-Stevenson, William G.

doi:10.1093/jnci/84.3.165

Cited by 161 publications

(120 citation statements)

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“…We also observed down-regulation of vimentin, which is commonly up-regulated in cancers, including HCC, and was shown to decrease significantly in HCC cells upon miR-122 expression (14,16). Vimentin is a marker for mesenchymal cells and is positively associated with invasiveness and metastatic potential (37)(38)(39). Although not previously identified as a direct target, the vimentin 3ЈUTR does contain a 7-mer-m8 seed site, suggesting it may indeed be a direct miR-122 target.…”

Section: Resultsmentioning

confidence: 63%

Two-tiered Approach Identifies a Network of Cancer and Liver Disease-related Genes Regulated by miR-122

Boutz

Collins

Suresh

et al. 2011

Journal of Biological Chemistry

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MicroRNAs function as important regulators of gene expression and are commonly linked to development, differentiation, and diseases such as cancer. To better understand their roles in various biological processes, identification of genes targeted by microRNAs is necessary. Although prediction tools have significantly helped with this task, experimental approaches are ultimately required for extensive target search and validation. We employed two independent yet complementary high throughput approaches to map a large set of mRNAs regulated by miR-122, a liver-specific microRNA implicated in regulation of fatty acid and cholesterol metabolism, hepatitis C infection, and hepatocellular carcinoma. The combination of luciferase reporterbased screening and shotgun proteomics resulted in the identification of 260 proteins significantly down-regulated in response to miR-122 in at least one method, 113 of which contain predicted miR-122 target sites. These proteins are enriched for functions associated with the cell cycle, differentiation, proliferation, and apoptosis. Among these miR-122-sensitive proteins, we identified a large group with strong connections to liver metabolism, diseases, and hepatocellular carcinoma. Additional analyses, including examination of consensus binding motifs for both miR-122 and target sequences, provide further insight into miR-122 function. MicroRNAs (miRNAs)4 are small (20 -24 nt) endogenously expressed noncoding RNAs that regulate the translational efficiency and/or degradation of specific mRNAs. First discovered in Caenorhabditis elegans (1), miRNAs have since been identified in a diverse set of eukaryotic organisms as well as viruses, with over 700 miRNAs currently identified in humans (2). miRNAs function via the RNAi pathway, guiding the RNAinduced silencing complex to mRNAs by Watson-Crick base pairing between the miRNA and target mRNA (reviewed in Ref.3). The resulting interaction leads to translational repression of the mRNA, although how this repression is achieved remains unclear. Several mechanisms have been proposed (reviewed in Ref. 4), and many questions remain; however, it is clear that sequence complementarity lies at the heart of miRNA function. In animals, sequence complementarity between an miRNA and its target mRNA is rarely perfect. The vast majority of binding sites contain mismatches between strands, and these mismatches have been shown to play an important functional role in target repression (5, 6). Imperfect complementarity allows for a greater variability of target sequences, thus increasing the number of potential binding sites for a given miRNA, with estimates of 300 -400 targets on average per miRNA (7). Although many potential miRNA targets can be identified through predictions, no computational approach is all-inclusive, and even highly conservative predictions must be validated by experimental means to verify functional relevance.Certain miRNAs have caught the attention of scientists due to their strong connections to diseases and cancer. Such is the

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Section: Resultsmentioning

confidence: 63%

Two-tiered Approach Identifies a Network of Cancer and Liver Disease-related Genes Regulated by miR-122

Boutz

Collins

Suresh

et al. 2011

Journal of Biological Chemistry

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“…Many epithelial cells express cytokeratin proteins K8, K18 and K19 (Oshima et al, 1988). Overexpression of cytokeratins with vimentin can lead to increased cell migration (Thompson et al, 1992;Chu et al, 1996), while overexpression of a dominant negative mutant K18 has been reported to reduce migratory ability in melanoma cells (Hendrix et al, 1992). These data raise the possibility that BAG-1 may promote cell migration through cooperation with these cytoskeletal proteins.…”

Section: Discussionmentioning

confidence: 98%

BAG-1 accelerates cell motility of human gastric cancer cells

et al. 1999

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“…The human cutaneous (C81-61 and C8161) and uveal melanoma (OCM-1A, C918, MUM-2B, and MUM-2C) cell lines have been characterized previously according to their phenotype, invasive and metastatic potential, and clinical significance. C8161, C918, and MUM-2B cells are highly aggressive, whereas C81-61, OCM-1A, and MUM-2C are poorly aggressive melanoma cells (6,14,15). Human umbilical vein endothelial cells (HUVECs) were maintained in DMEM, 10% FBS, 1ϫ Mitoϩ (Collaborative Biomedical, Bedford, MA), and 0.1% gentamicin sulfate.…”

Section: Methodsmentioning

confidence: 99%

“…The protein concentration in whole-cell lysates from the different cultures were determined by using a microbicinchoninic acid protein assay (BCA, Pierce) and equal amounts of protein for each cell line loaded onto 7.5% reducing sodium-dodecylsulfate polyacrylamide gels for electrophoresis. The separated proteins were transblotted onto Immobilon-P membranes (Millipore), which subsequently were probed with antibodies to human VE-cadherin (Transduction Laboratories, Lexington, KY), CD-31, or TIE-1 (R&D Systems), and detected as described (14).…”

Section: Methodsmentioning

confidence: 99%

Expression and functional significance of VE-cadherin in aggressive human melanoma cells: Role in vasculogenic mimicry

Hendrix

Seftor

Meltzer

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

416

370

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We recently have introduced the term vasculogenic mimicry to describe the unique ability of aggressive melanoma tumor cells to form tubular structures and patterned networks in three-dimensional culture, which ''mimics'' embryonic vasculogenic networks formed by differentiating endothelial cells. In the current study, we address the biological significance of several endothelial-associated molecules (revealed by microarray analysis) with respect to expression and function in highly aggressive and poorly aggressive human cutaneous melanoma cell lines (established from the same patient). In a comparative analysis, CD31 was not expressed by any of the melanoma cell lines, whereas TIE-1 (tyrosine kinase with Ig and epidermal growth factor homology domains-1) was strongly expressed

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Coexpression of Vimentin and Keratins by Human Melanoma Tumor Cells: Correlation With Invasive and Metastatic Potential

Abstract: These findings show a correlation between the coexpression of vimentin with K8 and K18 keratins and the invasive and metastatic behavior of three representative human melanoma cell lines.

Cited by 161 publications

References 0 publications

Two-tiered Approach Identifies a Network of Cancer and Liver Disease-related Genes Regulated by miR-122

Two-tiered Approach Identifies a Network of Cancer and Liver Disease-related Genes Regulated by miR-122

BAG-1 accelerates cell motility of human gastric cancer cells

Expression and functional significance of VE-cadherin in aggressive human melanoma cells: Role in vasculogenic mimicry

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