Aneuploidy facilitates oncogenic transformation via specific genetic alterations, including Twist2 upregulation

Gunilla Högnäs, Saara Hämälistö, Kirsi Rilla, Jukka O. Laine, Vesa Vilkki, Astrid Murumägi, Henrik Edgren, Olli Kallioniemi, Johanna Ivaska (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

2 Citations (Scopus)

Abstract

Aneuploidy, deviation from the normal chromosome number, and other chromosomal aberrations are commonly observed in cancer. Integrin-mediated adhesion and dynamic turnover of adhesion sites are required for successful cytokinesis of normal adherent cells and impaired cell division can lead to the generation of cells with abnormal chromosome contents. We find that repeated cytokinesis failure, due to impaired integrin traffic alone, is sufficient to induce chromosome aberrations resulting in the generation of aneuploid cells with malignant properties. Here, we have compared isogenic aneuploid and euploid cell lines with unravel aneuploidy-induced changes in cellular signaling. Euploid, non-transformed, and aneuploid, transformed, cell lines were investigated using genome-wide gene expression profiling, analysis of deregulated biological pathways and array-comparative genomic hybridization. We find that aneuploidy drives malignancy via inducing marked changes in gene and micro RNA expression profiles and thus imposing specific growth and survival promoting alterations in cellular signaling. Importantly, we identify Twist2 as a key regulator of survival, invasion and anchorage-independent growth in the aneuploid cells. In addition, alterations in lipid biosynthetic pathways and miR-10b upregulation are likely contributors to the malignant phenotype.
Original languageEnglish
Pages (from-to)2000-2009
JournalCarcinogenesis
Volume34
Issue number9
DOIs
Publication statusPublished - 2013
MoE publication typeA1 Journal article-refereed

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Aneuploidy
Up-Regulation
Cytokinesis
Integrins
Chromosome Aberrations
Chromosomes
Transformed Cell Line
Comparative Genomic Hybridization
Biosynthetic Pathways
Gene Expression Profiling
Growth
MicroRNAs
Cell Division
Neoplasms
Genome
Phenotype
Lipids
Cell Line
Genes

Cite this

Högnäs, G., Hämälistö, S., Rilla, K., Laine, J. O., Vilkki, V., Murumägi, A., ... Ivaska, J. (2013). Aneuploidy facilitates oncogenic transformation via specific genetic alterations, including Twist2 upregulation. Carcinogenesis, 34(9), 2000-2009. https://doi.org/10.1093/carcin/bgt171
Högnäs, Gunilla ; Hämälistö, Saara ; Rilla, Kirsi ; Laine, Jukka O. ; Vilkki, Vesa ; Murumägi, Astrid ; Edgren, Henrik ; Kallioniemi, Olli ; Ivaska, Johanna. / Aneuploidy facilitates oncogenic transformation via specific genetic alterations, including Twist2 upregulation. In: Carcinogenesis. 2013 ; Vol. 34, No. 9. pp. 2000-2009.
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abstract = "Aneuploidy, deviation from the normal chromosome number, and other chromosomal aberrations are commonly observed in cancer. Integrin-mediated adhesion and dynamic turnover of adhesion sites are required for successful cytokinesis of normal adherent cells and impaired cell division can lead to the generation of cells with abnormal chromosome contents. We find that repeated cytokinesis failure, due to impaired integrin traffic alone, is sufficient to induce chromosome aberrations resulting in the generation of aneuploid cells with malignant properties. Here, we have compared isogenic aneuploid and euploid cell lines with unravel aneuploidy-induced changes in cellular signaling. Euploid, non-transformed, and aneuploid, transformed, cell lines were investigated using genome-wide gene expression profiling, analysis of deregulated biological pathways and array-comparative genomic hybridization. We find that aneuploidy drives malignancy via inducing marked changes in gene and micro RNA expression profiles and thus imposing specific growth and survival promoting alterations in cellular signaling. Importantly, we identify Twist2 as a key regulator of survival, invasion and anchorage-independent growth in the aneuploid cells. In addition, alterations in lipid biosynthetic pathways and miR-10b upregulation are likely contributors to the malignant phenotype.",
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Högnäs, G, Hämälistö, S, Rilla, K, Laine, JO, Vilkki, V, Murumägi, A, Edgren, H, Kallioniemi, O & Ivaska, J 2013, 'Aneuploidy facilitates oncogenic transformation via specific genetic alterations, including Twist2 upregulation', Carcinogenesis, vol. 34, no. 9, pp. 2000-2009. https://doi.org/10.1093/carcin/bgt171

Aneuploidy facilitates oncogenic transformation via specific genetic alterations, including Twist2 upregulation. / Högnäs, Gunilla; Hämälistö, Saara; Rilla, Kirsi; Laine, Jukka O.; Vilkki, Vesa; Murumägi, Astrid; Edgren, Henrik; Kallioniemi, Olli; Ivaska, Johanna (Corresponding Author).

In: Carcinogenesis, Vol. 34, No. 9, 2013, p. 2000-2009.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Aneuploidy facilitates oncogenic transformation via specific genetic alterations, including Twist2 upregulation

AU - Högnäs, Gunilla

AU - Hämälistö, Saara

AU - Rilla, Kirsi

AU - Laine, Jukka O.

AU - Vilkki, Vesa

AU - Murumägi, Astrid

AU - Edgren, Henrik

AU - Kallioniemi, Olli

AU - Ivaska, Johanna

PY - 2013

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AB - Aneuploidy, deviation from the normal chromosome number, and other chromosomal aberrations are commonly observed in cancer. Integrin-mediated adhesion and dynamic turnover of adhesion sites are required for successful cytokinesis of normal adherent cells and impaired cell division can lead to the generation of cells with abnormal chromosome contents. We find that repeated cytokinesis failure, due to impaired integrin traffic alone, is sufficient to induce chromosome aberrations resulting in the generation of aneuploid cells with malignant properties. Here, we have compared isogenic aneuploid and euploid cell lines with unravel aneuploidy-induced changes in cellular signaling. Euploid, non-transformed, and aneuploid, transformed, cell lines were investigated using genome-wide gene expression profiling, analysis of deregulated biological pathways and array-comparative genomic hybridization. We find that aneuploidy drives malignancy via inducing marked changes in gene and micro RNA expression profiles and thus imposing specific growth and survival promoting alterations in cellular signaling. Importantly, we identify Twist2 as a key regulator of survival, invasion and anchorage-independent growth in the aneuploid cells. In addition, alterations in lipid biosynthetic pathways and miR-10b upregulation are likely contributors to the malignant phenotype.

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DO - 10.1093/carcin/bgt171

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SP - 2000

EP - 2009

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 9

ER -