(A) MCF7-ARO cells treated with DMSO, single agent taselisib or letrozole plus media or 50 ng/ml of one of 418 secreted factors, and assayed for viability using Cell-TiterGlo. Controls in the absence of secreted factors in the presence or absence of taselisib are indicated. (B) Confirmation of factors that rescue growth inhibition by letrozole. MCF7-ARO cells treated with taselisib (top) or letrozole (bottom) plus 50 ng/ml of the indicated secreted factors, and assayed for viability using CellTiter-Glo. (C) Many of the secreted factors signal down the PI3K pathway. MCF7-ARO cells simulated with 50 ng/ml of the indicated secreted factors in the presence of DMSO, 0.6 μM taselisib, 1 μM letrozole or a combination of the two drugs. After 1 hr, cell lysates were prepared and analyzed by immunoblotting for pERKT202/Y204, pAKTS473, pERαS118, pERαS167,pSTAT3Y705, and βActin. For viability experiments, error bars indicate standard deviation around the mean.