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, Emma Lundberg

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Abstract

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.
Original languageEnglish
JournalOncoTarget
Volume9
Issue number28
Pages (from-to)19730-19744
ISSN1949-2553
DOIs
Publication statusPublished - 2018

Keywords

  • Hypoxia
  • Transcriptomics
  • Malignant transformation

Cite this

Danielsson, F., Fasterius, E., Sullivan, D., Hases, L., Sanli, K., Zhang, C., ... Lundberg, E. (2018). Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia. OncoTarget, 9(28), 19730-19744. https://doi.org/10.18632/oncotarget.24808
Danielsson, Frida ; Fasterius, Erik ; Sullivan, Devin ; Hases, Linnea ; Sanli, Kemal ; Zhang, Cheng ; Mardinoglu, Adil ; Al-Khalili, Cristina ; Huss, Mikael ; Uhlén, Mathias ; Williams, Cecilia ; Lundberg, Emma. / Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia. In: OncoTarget. 2018 ; Vol. 9, No. 28. pp. 19730-19744.
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abstract = "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.",
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Danielsson, F, Fasterius, E, Sullivan, D, Hases, L, Sanli, K, Zhang, C, Mardinoglu, A, Al-Khalili, C, Huss, M, Uhlén, M, Williams, C & Lundberg, E 2018, 'Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia', OncoTarget, vol. 9, no. 28, pp. 19730-19744. https://doi.org/10.18632/oncotarget.24808

Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia. / Danielsson, Frida; Fasterius, Erik; Sullivan, Devin; Hases, Linnea; Sanli, Kemal; Zhang, Cheng; Mardinoglu, Adil; Al-Khalili, Cristina; Huss, Mikael; Uhlén, Mathias; Williams, Cecilia; Lundberg, Emma.

In: OncoTarget, Vol. 9, No. 28, 2018, p. 19730-19744.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia

AU - Danielsson, Frida

AU - Fasterius, Erik

AU - Sullivan, Devin

AU - Hases, Linnea

AU - Sanli, Kemal

AU - Zhang, Cheng

AU - Mardinoglu, Adil

AU - Al-Khalili, Cristina

AU - Huss, Mikael

AU - Uhlén, Mathias

AU - Williams, Cecilia

AU - Lundberg, Emma

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Hypoxia

KW - Transcriptomics

KW - Malignant transformation

U2 - 10.18632/oncotarget.24808

DO - 10.18632/oncotarget.24808

M3 - Journal article

VL - 9

SP - 19730

EP - 19744

JO - OncoTarget

JF - OncoTarget

SN - 1949-2553

IS - 28

ER -