DDX17 (P72), a Sox2 binding partner, regulates Sox2 to sustain tumorigenic and stem-like properties in a phenotypically distinct subset of estrogen positive breast cancer cells

• DDX17 (P72), a Sox2 binding partner, promotes stem-like features conferred by Sox2 in a small cell population in estrogen receptor-positive breast cancer

• Author / Creator

  Alqahtani,Hind M

• Abstract: Sox2, an embryonic stem cell marker, is involved in the pathogenesis of breast cancer (BC). Sox2 expression is associated with a poor clinical outcome in BC patients. Based on the differential Sox2 transcriptional activity, we have identified the two phenotypically distinct cell subsets, namely reporter responsive (RR) and reporter unresponsive (RU) cells. RR cells are more tumorigenic and stem-like than RU cells. The goal of this study is to understand the mechanisms of regulating Sox2 transcriptional activity. By using liquid chromatography–mass spectrometry and co-immunoprecipitation, we found that DDX17 is a Sox2 binding partner in ER+ BC cell lines. The interaction between DDX17 and Sox2 was found to be significantly higher in the RR cell subset than in the RU subset. DDX17 was found to bind to the Sox2 promoter and regulate its expression in RR cells derived from the MCF7 cell line. Although, the protein level of Sox2 was unaffected in RU and RR cell subsets. Upon siRNA knockdown of DDX17, the transcriptional activity of Sox2 was significantly decreased in RR cells but not in RU cells. Correlating with these findings, siRNA knockdown of DDX17 drastically reduced the tumorigenic and stem-like properties in RR cells, as observed by decreased in colony formation and mammosphere formation efficiency. In conclusion, DDX17 regulates Sox2 to maintain tumorigenic and stem-like properties. The interaction between Sox2 and DDX17 provides a novel mechanism underlying the functional dichotomy of BC cells, which carries potential therapeutic implications

• Subjects / Keywords

  • Transcriptional activity
  • Breast cancer
  • DDX17
  • Sox2

• Graduation date

  Spring 2016

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3J67948X

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.