title: A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness.
abstract: Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from non-invasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes in cellular invasiveness from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion. Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness.
  
  
  CONCLUSIONS
  Our study provides evidence that common DNA hypomethylation signature exists between cancer cells derived from different tissues, pointing to a common mechanism of cancer invasiveness in cancer cells from different origins that could serve as drug targets.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Cheishvili
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.|Department of Nutrition Science, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Stefanska
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: Cao
authors.initials: C
authors.lastname: Yi
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: Chen Chen
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Yu
authors.affiliation: Departments of Medicine, Oncology, and Pharmacology, McGill University, Montreal, Quebec, Canada.
authors.forename: Ani
authors.initials: A
authors.lastname: Arakelian
authors.affiliation: Department of Pathology, Fatima Memorial Hospital System, Lahore, Pakistan.
authors.forename: Imrana
authors.initials: I
authors.lastname: Tanvir
authors.affiliation: Department of Pathology, Fatima Memorial Hospital System, Lahore, Pakistan.
authors.forename: Haseeb Ahmed
authors.initials: HA
authors.lastname: Khan
authors.affiliation: Departments of Medicine, Oncology, and Pharmacology, McGill University, Montreal, Quebec, Canada.
authors.forename: Shafaat
authors.initials: S
authors.lastname: Rabbani
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.|Department of Pharmacology and Therapeutics, Sackler Program for Epigenetics & Developmental Psychobiology, McGill University Medical School, Montreal, Quebec, Canada.|Department of Pharmacology and Therapeutics, Canadian Institute for Advanced Research, Montreal, Quebec, Canada.
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D061986:MCF-7 Cells; D008297:Male; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology; D059467:Transcriptome
keywords: DNA methylation; drug targets; epigenetics; hypomethylation; invasiveness