Upregulation of endogenous ICAM‐1 reduces ovarian cancer cell growth in the absence of immune cells

Groote, Marloes L. de; Kazemier, Hinke G.; Huisman, Christian; Gun, Bernardina T. F. van der; Faas, Marijke M.; Rots, Marianne G.

doi:10.1002/ijc.28375

Cited by 33 publications

(23 citation statements)

References 45 publications

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“…The CD54-31Opt was chosen because it was shown to effectively target the ICAM1 promoter, altering transcription levels when fused to transcriptional activators or repressors [50], [51]. Additionally, fusion of CD54-31Opt to Ten-Eleven Translocation 2 enzyme resulted in a small, observable amount of demethylation around the target site, correlating with a 2-fold upregulation in ICAM1 transcription [52].…”

Section: Resultsmentioning

confidence: 99%

Directed Evolution of Improved Zinc Finger Methyltransferases

Chaikind

Ostermeier

2014

PLoS ONE

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The ability to target DNA methylation toward a single, user-designated CpG site in vivo may have wide applicability for basic biological and biomedical research. A tool for targeting methylation toward single sites could be used to study the effects of individual methylation events on transcription, protein recruitment to DNA, and the dynamics of such epigenetic alterations. Although various tools for directing methylation to promoters exist, none offers the ability to localize methylation solely to a single CpG site. In our ongoing research to create such a tool, we have pursued a strategy employing artificially bifurcated DNA methyltransferases; each methyltransferase fragment is fused to zinc finger proteins with affinity for sequences flanking a targeted CpG site for methylation. We sought to improve the targeting of these enzymes by reducing the methyltransferase activity at non-targeted sites while maintaining high levels of activity at a targeted site. Here we demonstrate an in vitro directed evolution selection strategy to improve methyltransferase specificity and use it to optimize an engineered zinc finger methyltransferase derived from M.SssI. The unusual restriction enzyme McrBC is a key component of this strategy and is used to select against methyltransferases that methylate multiple sites on a plasmid. This strategy allowed us to quickly identify mutants with high levels of methylation at the target site (up to ∼80%) and nearly unobservable levels of methylation at a off-target sites (<1%), as assessed in E. coli. We also demonstrate that replacing the zinc finger domains with new zinc fingers redirects the methylation to a new target CpG site flanked by the corresponding zinc finger binding sequences.

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Section: Resultsmentioning

confidence: 99%

Directed Evolution of Improved Zinc Finger Methyltransferases

Chaikind

Ostermeier

2014

PLoS ONE

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“…Furthermore, expression of ICAM1 is highly variable in cancer, being up-regulated in breast, gastric, melanoma, gall bladder, and colon cancers [45], [46] and down-regulated in ovarian [47] and gastric [48] cancers. MCAM is another IgSF-CAM that was uniquely and highly expressed in the MDA-MB-231 cells.…”

Section: Resultsmentioning

confidence: 99%

Plasma Membrane Proteomics of Human Breast Cancer Cell Lines Identifies Potential Targets for Breast Cancer Diagnosis and Treatment

Ziegler

Moresco

et al. 2014

PLoS ONE

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The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease.

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“…In melanoma and gastric cancer, ICAM1 expression was associated with an increase in metastases [79, 80]. This can be explained by ICAM1-mediated activation of leukocytes and induction of cell migration [81]. On the other hand, immunohistochemistry studies reported better prognosis for patients with ICAM1-positive tumors (including lymphoma, ovarian, colorectal, head and neck cancers) [82–84].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer

et al. 2016

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BackgroundColorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC.ResultsUsing CrossHub software, we analyzed The Cancer Genome Atlas (TCGA) RNA-Seq datasets derived from colon tumor and matched normal tissues. The expression of 1014 alternative mRNA isoforms involved in cell energy metabolism was examined. We found 7 genes with differentially expressed alternative transcripts whereas overall expression of these genes was not significantly altered in CRC. A set of 8 differentially expressed transcripts of interest has been validated by qPCR. These eight isoforms encoded by OGDH, COL6A3, ICAM1, PHPT1, PPP2R5D, SLC29A1, and TRIB3 genes were up-regulated in colorectal tumors, and this is in concordance with the bioinformatics data. The alternative transcript NM_057167 of COL6A3 was also strongly up-regulated in breast, lung, prostate, and kidney tumors. Alternative transcript of SLC29A1 (NM_001078177) was up-regulated only in CRC samples, but not in the other tested tumor types.ConclusionsWe identified tumor-specific expression of alternative spliced transcripts of seven genes involved in energy metabolism in CRC. Our results bring new knowledge on alternative splicing in colorectal cancer and suggest a set of mRNA isoforms that could be used for cancer diagnosis and development of treatment methods.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3351-5) contains supplementary material, which is available to authorized users.

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Upregulation of endogenous ICAM‐1 reduces ovarian cancer cell growth in the absence of immune cells

Cited by 33 publications

References 45 publications

Directed Evolution of Improved Zinc Finger Methyltransferases

Directed Evolution of Improved Zinc Finger Methyltransferases

Plasma Membrane Proteomics of Human Breast Cancer Cell Lines Identifies Potential Targets for Breast Cancer Diagnosis and Treatment

Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer

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