Fig. 2.

Overview of the Notch and Hedgehog signaling pathways in CSCs. Peripheral tumor cells, CSCs, and mesenchymal cells can initiate the transcription of stemness genes (NANOG, Oct4, Sox2, and Bmi1) in CSCs through Hedgehog signaling to maintain stem cell properties. The role of the Notch and Hedgehog signaling pathways is demonstrated in the zoomed-in CSC on the right side of the figure. S1P enhances CSC activity by binding S1PR secondary to Notch activation. The Hedgehog and Notch pathways also increase ABC-transporters, which increases drug efflux and leads to chemoresistance. The Hedgehog and Notch pathways also increase ROS further affecting the efficacy of subsequent drug and radiation therapy