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

16 Scopus citations

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

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells'. Together they form a unique fingerprint.

  • Cite this

    Braune, E. B., Tsoi, Y. L., Phoon, Y. P., Landor, S., Silva Cascales, H., Ramsköld, D., Deng, Q., Lindqvist, A., Lian, X., Sahlgren, C., Jin, S. B., & 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