Differential phase register of Hes1 oscillations with mitoses underlies cell-cycle heterogeneity in ER <sup>+</sup> breast cancer cells
Nitin Sabherwal, Andrew Rowntree, Elli Marinopoulou, Tom Pettini, Sean Hourihane, Riba Thomas, Ximena Soto, Jochen Kursawe, Nancy Papalopulu
Abstract
Significance Tumors exhibit heterogeneities that are not due to mutations, including cancer stem cells with different potencies. We show that the cancer stem-cell state predisposed to dormancy in vivo has a highly variable and long cell cycle. Using single-cell live imaging for the transcriptional repressor Hes1 (a key molecule in cancer), we show a type of circadian-like oscillatory expression of Hes1 in all cells in the population. The most potent cancer stem cells tend to divide around the trough of the Hes1 oscillatory wave, a feature predictive of a long cell cycle. A concept proposed here is that the position of cell division with respect to the Hes1 wave is predictive of its prospective cell-cycle length and cancer cellular substate.