Supplement 1 -Psen1 -Psen2 Dasatinib (100 nM) Hours Con

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Supplement 1 -Psen1 -Psen2 Dasatinib (100 nM) Hours Con 24 48 72 -cyclin D1 -Psen1 -Psen2 - Trop2- ICD -Vinculin

A B C Supplement 2 -Psen1 -Psen2 DMSO Canertinib 200 m 24 h 48 h 40 80 120 DMSO Canertinib Canertinib Canertinib Canertinib DMSO DMSO DMSO Cell number per 104 m2 -cyclin D1 -Psen1 -Psen2 - Trop2- ICD -Vinculin

Supplement 3 Trop2 TACE ECD γ-Secretase ICD PS1 PS2 Numb Nucleus Src Cyclin D1 Stem Cell Population Numb γ-Secretase PS1 PS2 Nucleus

Human prostate cancer TMA IHC Supplement 4 Human prostate cancer TMA IHC High expression Low expression Cyclin D1 Trop-ICD Presenilin 2 Numb