Research Papers:

Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia

Frida Danielsson, Erik Fasterius, Devin Sullivan, Linnea Hases, Kemal Sanli, Cheng Zhang, Adil Mardinoglu, Cristina Al-Khalili, Mikael Huss, Mathias Uhlén, Cecilia Williams and Emma Lundberg _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2018; 9:19730-19744. https://doi.org/10.18632/oncotarget.24808

Metrics: PDF 1856 views  |   HTML 4135 views  |   ?  


Frida Danielsson1, Erik Fasterius2, Devin Sullivan1, Linnea Hases1,5, Kemal Sanli1, Cheng Zhang1, Adil Mardinoglu1, Cristina Al-Khalili2, Mikael Huss3, Mathias Uhlén1,2,4, Cecilia Williams1,5 and Emma Lundberg1

1Science for Life Laboratory, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm SE-171 21, Sweden

2Department of Proteomics, KTH, Royal Institute of Technology, Stockholm SE-106 91, Sweden

3Department of Biochemistry and Biophysics, Stockholm University, Solna SE-171 21, Sweden

4Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm DK-2970, Denmark

5Department of Biosciences and Nutrition, Karolinska Institute, Huddinge SE-141 57, Sweden

Correspondence to:

Emma Lundberg, email: [email protected]

Frida Danielsson, email: [email protected]

Keywords: hypoxia; transcriptomics; malignant transformation

Received: September 08, 2017     Accepted: February 24, 2018     Published: April 13, 2018


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 24808