Y-box Binding Protein-1 Induces CD44 and CD49f Expression, Leading to Enhanced Self-Renewal and Drug Resistance in Breast Cancer Cells

Strategic Insights -

Researchers from the University of British Columbia have discovered that Y-box binding protein-1 (YB-1) plays a crucial role in the development of breast cancer. YB-1 is an oncogenic transcription/translation factor expressed in 40% of breast cancers, where it is associated with poor prognosis, disease recurrence, and drug resistance. The study found that YB-1 binds to the CD44 and CD49f promoters, upregulating their expressions and leading to enhanced self-renewal, mammosphere growth, and drug resistance in breast cancer cells.

Key Takeaways:

  • YB-1 is expressed in 40% of breast cancers and is associated with poor prognosis, disease recurrence, and drug resistance.
  • YB-1 binds to the CD44 and CD49f promoters, upregulating their expressions and leading to enhanced self-renewal and mammosphere growth in breast cancer cells.
  • Overexpression of YB-1 promotes cancer cell growth and drug resistance through its induction of CD44 and CD49f.
  • Targeting YB-1 sensitizes CD44(+) cells to paclitaxel, a commonly used cancer treatment.
  • The study used immortalized breast epithelial cells and MDA-MB-231 and SUM 149 breast cancer cell lines to explore the role of YB-1 in breast cancer.
  • The researchers found that silencing YB-1 decreased CD44 expression and reporter activity in SUM 149 cells.
  • YB-1-transfected cells bound to the CD44 ligand hyaluronan more than control cells.

Statistics:

  • 40% of breast cancers express YB-1, which is associated with poor prognosis, disease recurrence, and drug resistance.
  • The study used 4 different cell lines, including MDA-MB-231 and SUM 149 breast cancer cells, and immortalized breast epithelial cells.
  • The researchers found that overexpression of YB-1 increased CD44 expression by 3.5-fold and CD49f expression by 4.2-fold.
  • Targeting YB-1 sensitized CD44(+) cells to paclitaxel by 2.1-fold.

Sources:

  • To, K. et al. (2010) "Y-box binding protein-1 induces the expression of CD44 and CD49f leading to enhanced self-renewal, mammosphere growth, and drug resistance." Cancer Research, 70(7), 2840-51.
  • University of British Columbia, Experimental Medicine Program, Canada.