BioProject

Differentiation events contribute to cellular heterogeneity within tumors and influence disease progression and response to therapy. More...

Differentiation events contribute to cellular heterogeneity within tumors and influence disease progression and response to therapy. Here we dissect mechanisms controlling intratumoral heterogeneity within triple-negative basal-like breast cancers. Tumor cells expressing the cytokeratin K14 possess a differentiation state that is associated with that of normal luminal progenitors, while K14-negative cells are in a state closer to that of mature luminal cells. We show that cells can transition between these states through asymmetric divisions, which produce one K14 + and one K14 – daughter cell, and that these asymmetric divisions contribute to the generation of cellular heterogeneity. We identified several regulators that control the proportion of K14 + cells in the population. EZH2 and Notch increase the numbers of K14 + cells and their rates of symmetric divisions, while FOXA1 has an opposing effect. Our findings demonstrate a role for asymmetric divisions as a mechanism for differentiation transitions, and identify

pathways that control breast cancer cellular composition. The data shows WGS of HCC70 cells sorted into K14-positive and K14-Negative populations. Less...