Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells

Eike Benjamin Braune, Yat Long Tsoi, Yee Peng Phoon, Sebastian Landor, Helena Silva Cascales, Daniel Ramsköld, Qiaolin Deng, Arne Lindqvist, Xiaojun Lian, Cecilia Sahlgren, Shao Bo Jin, Urban Lendahl

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Notch signaling is an important regulator of stem cell differentiation. All canonical Notch signaling is transmitted through the DNA-binding protein CSL, and hyperactivated Notch signaling is associated with tumor development; thus it may be anticipated that CSL deficiency should reduce tumor growth. In contrast, we report that genetic removal of CSL in breast tumor cells caused accelerated growth of xenografted tumors. Loss of CSL unleashed a hypoxic response during normoxic conditions, manifested by stabilization of the HIF1α protein and acquisition of a polyploid giant-cell, cancer stem cell-like, phenotype. At the transcriptome level, loss of CSL upregulated more than 1,750 genes and less than 3% of those genes were part of the Notch transcriptional signature. Collectively, this suggests that CSL exerts functions beyond serving as the central node in the Notch signaling cascade and reveals a role for CSL in tumorigenesis and regulation of the cellular hypoxic response.

Original languageEnglish (US)
Pages (from-to)643-651
Number of pages9
JournalStem Cell Reports
Volume6
Issue number5
DOIs
StatePublished - May 10 2016

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Tumors
Cells
Breast Neoplasms
Growth
Stem cells
Neoplasms
Polyploidy
Neoplastic Stem Cells
Genes
DNA-Binding Proteins
Giant Cells
Transcriptome
Cell Differentiation
Carcinogenesis
Stem Cells
Phenotype
Stabilization
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Braune, E. B., Tsoi, Y. L., Phoon, Y. P., Landor, S., Silva Cascales, H., Ramsköld, D., ... Lendahl, U. (2016). Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells. Stem Cell Reports, 6(5), 643-651. https://doi.org/10.1016/j.stemcr.2016.03.004
Braune, Eike Benjamin ; Tsoi, Yat Long ; Phoon, Yee Peng ; Landor, Sebastian ; Silva Cascales, Helena ; Ramsköld, Daniel ; Deng, Qiaolin ; Lindqvist, Arne ; Lian, Xiaojun ; Sahlgren, Cecilia ; Jin, Shao Bo ; Lendahl, Urban. / Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells. In: Stem Cell Reports. 2016 ; Vol. 6, No. 5. pp. 643-651.
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Braune, EB, Tsoi, YL, Phoon, YP, Landor, S, Silva Cascales, H, Ramsköld, D, Deng, Q, Lindqvist, A, Lian, X, Sahlgren, C, Jin, SB & Lendahl, U 2016, 'Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells', Stem Cell Reports, vol. 6, no. 5, pp. 643-651. https://doi.org/10.1016/j.stemcr.2016.03.004

Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells. / Braune, Eike Benjamin; Tsoi, Yat Long; Phoon, Yee Peng; Landor, Sebastian; Silva Cascales, Helena; Ramsköld, Daniel; Deng, Qiaolin; Lindqvist, Arne; Lian, Xiaojun; Sahlgren, Cecilia; Jin, Shao Bo; Lendahl, Urban.

In: Stem Cell Reports, Vol. 6, No. 5, 10.05.2016, p. 643-651.

Research output: Contribution to journalArticle

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Braune EB, Tsoi YL, Phoon YP, Landor S, Silva Cascales H, Ramsköld D et al. Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells. Stem Cell Reports. 2016 May 10;6(5):643-651. https://doi.org/10.1016/j.stemcr.2016.03.004