title: Deregulation of the replisome factor MCMBP prompts oncogenesis in colorectal carcinomas through chromosomal instability.
abstract: Genetic instability has emerged as an important hallmark of human neoplasia. Although most types of cancers exhibit genetic instability to some extent, in colorectal cancers genetic instability is a distinctive characteristic. Recent studies have shown that deregulation of genes involved in sister chromatid cohesion can result in chromosomal instability in colorectal cancers. Here, we show that the replisome factor minichromosome maintenance complex-binding protein (MCMBP), which is directly involved in the dynamics of the minichromosome maintenance complex and contributes to maintaining sister chromatid cohesion, is transcriptionally misregulated in different types of carcinomas. Cellular studies revealed that both MCMBP knockdown and overexpression in different breast and colorectal cell lines is associated with the emergence of a subpopulation of cells with abnormal nuclear morphology that likely arise as a consequence of aberrant cohesion events. Association analysis integrating gene expression data with clinical information revealed that enhanced MCMBP transcript levels correlate with an increased probability of relapse risk in colorectal cancers and different types of carcinomas. Moreover, a detailed study of a cohort of colorectal tumors showed that the MCMBP protein accumulates to high levels in cancer cells, whereas in normal proliferating tissue its abundance is low, indicating that MCMBP could be exploited as a novel diagnostic marker for this type of carcinoma.
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium; Department of Plant Systems Biology, VIB, 9052 Gent, Belgium; Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Gent, Belgium; Pontificia Universidad Javeriana Cali, Department of Natural Sciences and Mathematics, Cali, Colombia.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Quimbaya
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Raspé
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Geertrui
authors.initials: G
authors.lastname: Denecker
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: De Craene
authors.affiliation: Unit of Molecular Signaling and Cell Death, Department for Molecular Biomedical Research, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Ria
authors.initials: R
authors.lastname: Roelandt
authors.affiliation: Unit of Molecular Signaling and Cell Death, Department for Molecular Biomedical Research, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Declercq
authors.affiliation: Imaging and Pathology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sagaert
authors.affiliation: Department of Plant Systems Biology, VIB, 9052 Gent, Belgium; Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Gent, Belgium.
authors.forename: Lieven
authors.initials: L
authors.lastname: De Veylder
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium. Electronic address: Geert.Berx@irc.vib-UGent.be.
authors.forename: Geert
authors.initials: G
authors.lastname: Berx
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism*; D043171:Chromosomal Instability; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006657:Histones; C519407:MCMBP protein, human; D009687:Nuclear Proteins