Selective PROTAC-mediated degradation and shRNA-driven knockdown of SMARCA2 in HCC2302 lung adenocarcinoma cells

SMARCA2 and SMARCA4 are mutually-exclusive, core catalytic subunits for the chromatin remodeling SWI/SNF complex. Mutations in SMARCA4 are common in lung adenocarcinoma and have shown synthetic lethality with loss of SMARCA2 loss of function. The purpose of this project is to answer questions related to the in vivo [mouse xenograft] efficacy of A947, a SMARCA2 degrader. The study involves in vitro versus in vivo comparisons of drug activity, in addition to genetic manipulation of the target. Model system: HCC2302 (RRID:CVCL_V636); Model origin: Lung Adenocarcinoma; Perturbation: A947 (VHL-PROTAC-based degrader) in vitro samples are treated with either a non-targeting shRNA (in vitro HCC2302-shNTC) or a SMARCA2-targeting shRNA (in vitro HCC2302-shSMARCA2-dual62 cl2), both of which are doxycycline-inducible. Vehicle (non-induced) samples are labeled as "Veh" and doxycycline-induced samples are labeled as "Dox." in vivo mouse xenograft samples (in vivo mouse xenograft HCC2302) are treated with either vehicle (Veh) or A947 (A947). There are 3 replicates per in vitro condition and 5 replicates per in vivo condition.