Figure 6.

Schematic shows breast cancer cell population phenotype changes under drug stress toward a drug tolerant state arising through translocation of CD24 and sustained p38 activation. (a) In proliferative conditions, CD24 is mainly detected in the cytosol of all cells and the population is characterized by a low frequency of CD24⁺ cells (cells carrying CD24 in membrane). The transient phosphorylation of p38 leads to cyclin D1 expression and cell cycle progression. (b) Under drug treatment, CD24 translocation associated with an increased CD24 density on cell membrane occurs in every given cell. In accord with this, a sustained and strong p38 activation, an increased Bcl-2 expression are observed indicating a phenotype switching. (c) This transition state is sensitive to p38 inhibition since the use of a specific inhibitor, like SB203580, in association with doxorubicin reduces Bcl-2 expression leading to an increased cell death.