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Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia
KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-7692-1100
KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
KTH, Centres, Science for Life Laboratory, SciLifeLab.
KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Institute, Huddinge, Sweden.
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2018 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 28, p. 19730-19744Article in journal (Refereed) Published
Abstract [en]

In tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing their surrounding vasculature network. Transformed cancer cells are known to exhibit phenotypic alterations, enabling continuous proliferation despite a limited oxygen supply. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and moderate hypoxic (3% O2) conditions, we observed that despite being highly similar, the four cell lines of the BJ model responded strikingly different to hypoxia. Besides corroborating many of the known responses to hypoxia, we demonstrate that the transcriptome adaptation to moderate hypoxia resembles the process of malignant transformation. The transformed cells displayed a distinct capability of metabolic switching, reflected in reversed gene expression patterns for several genes involved in oxidative phosphorylation and glycolytic pathways. By profiling the stage-specific responses to hypoxia, we identified ASS1 as a potential prognostic marker in hypoxic tumors. This study demonstrates the usefulness of the BJ cell model for highlighting the interconnection of pathways involved in malignant transformation and hypoxic response.

Place, publisher, year, edition, pages
Impact Journals LLC , 2018. Vol. 9, no 28, p. 19730-19744
Keywords [en]
Hypoxia, Malignant transformation, Transcriptomics
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-227616DOI: 10.18632/oncotarget.24808Scopus ID: 2-s2.0-85045315705OAI: oai:DiVA.org:kth-227616DiVA, id: diva2:1209147
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180522

Available from: 2018-05-22 Created: 2018-05-22 Last updated: 2018-05-22Bibliographically approved

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Danielsson, FridaFasterius, ErikSanli, KemalZhang, ChengMardinoglu, AdilAl-Khalili Szigyarto, CristinaUhlén, MathiasWilliams, CeciliaLundberg, Emma

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Danielsson, FridaFasterius, ErikSullivan, DevinHases, LinneaSanli, KemalZhang, ChengMardinoglu, AdilAl-Khalili Szigyarto, CristinaUhlén, MathiasWilliams, CeciliaLundberg, Emma
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Science for Life Laboratory, SciLifeLabProteomics (closed 20130101)
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