Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state

Current models of stem cell biology assume that normal and neoplastic stem cells reside at the apices of hierarchies and differentiate into nonstem progeny in a unidirectional manner. Here we identify a subpopulation of basal-like human mammary epithelial cells that departs from that assumption, spontaneously dedifferentiating into stem-like cells. Moreover, oncogenic transformation enhances the spontaneous conversion, so that nonstem cancer cells give rise to cancer stem cell (CSC)-like cells in vitro and in vivo. We further show that the differentiation state of normal cells-of-origin is a strong determinant of posttransformation behavior. These findings demonstrate that normal and CSC-like cells can arise…

• UD
  U.S. Department of Defense
• BC
  Breast Cancer Research Foundation
• AM
  Advanced Medical Research Foundation
• MI
  Massachusetts Institute of Technology
• KI
  Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
• NI
  National Institutes of Health
• LC
  Ludwig Center at Harvard
• MR
  Medical Research Council
• NH
  National Health and Medical Research Council