KEY RESOURCES TABLE
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
|---|---|---|
| Antibodies | ||
| Rabbit polyclonal anti-BIM (22–40) | EMD Biosciences | Cat# 202000; RRID: AB_565367 |
| Rabbit polyclonal anti-BIM (22–40) | Covance | COVQ21008 |
| Rabbit monoclonal anti-PUMA (D30C10) | Cell Signaling Technology | Cat# 12450; RRID: AB_2797920 |
| Hamster monoclonal anti-BCL-2 (6C8) | BD Biosciences | Cat# 551051; RRID: AB_394018 |
| Rabbit polyclonal anti-BCL-XL | Cell Signaling Technology | Cat# 2762; RRID: AB_10694844 |
| Rabbit polyclonal anti-MCL-1 (S-19) | Santa Cruz Biotechnology | Cat# sc-819; RRID: AB_2144105 |
| Rabbit polyclonal anti-BAX | Cell Signaling Technology | Cat# 2772; RRID: AB_10695870 |
| Rabbit monoclonal anti-BAK (D4E4) | Cell Signaling Technology | Cat# 12105; RRID: AB_2716685 |
| Rabbit monoclonal anti-phospho AKT (Ser473) | Cell Signaling Technology | Cat# 4058; RRID: AB_331168 |
| Rabbit polyclonal anti-AKT | Cell Signaling Technology | Cat# 9272; RRID: AB_329827 |
| Rabbit polyclonal anti-phospho ERK1/2 | Cell Signaling Technology | Cat# 9101; RRID: AB_331646 |
| Mouse monoclonal anti-ERK1/2 (3A7) | Cell Signaling Technology | Cat# 9107; RRID: AB_10695739 |
| Rabbit polyclonal anti-phospho BIM (Ser69) | Cell Signaling Technology | Cat# 4581; RRID: AB_2065179 |
| Rabbit polyclonal anti-phospho BIM (Ser87) | Bioss Inc | Cat# bs-3012R |
| Rabbit polyclonal anti-phospho FOXO1/3 (Thr24/Thr32) | Cell Signaling Technology | Cat# 9464; RRID: AB_329842 |
| Rabbit monoclonal anti-FOXO1 (C29H4) | Cell Signaling Technology | Cat# 2880; RRID: AB_2106495 |
| Rabbit polyclonal anti-FOXO3 | Millipore | Cat# 07–702; RRID: AB_441949 |
| Mouse monoclonal anti-ZEB1 (H-3) | Santa Cruz Biotechnology | Cat# sc-515797 |
| Mouse monoclonal anti-ZEB2 (E-11) | Santa Cruz Biotechnology | Cat# sc-271984; RRID: AB_10708399 |
| Mouse monoclonal anti-E-cadherin | BD Biosciences | Cat# 610182; RRID: AB_397581 |
| Rabbit monoclonal anti-Vimentin (D21H3) | Cell Signaling Technology | Cat# 5741; RRID: AB_10695459 |
| Rabbit monoclonal anti-AURKA (D3E4Q) | Cell Signaling Technology | Cat# 14475; RRID: AB_2665504 |
| Rabbit polyclonal anti-AURKB | Cell Signaling Technology | Cat# 3094; RRID: AB_10695307 |
| Rabbit monoclonal anti-phospho AURKA/AURKB/AURKC (Thr288/Thr232/Thr398) | Cell Signaling Technology | Cat# 2914; RRID: AB_2061631 |
| Mouse monoclonal anti-Histone H3 (1B1B2) | Cell Signaling Technology | Cat# 14269; RRID: AB_2756816 |
| Rabbit polyclonal anti-phospho Histone H3 (Ser10) | Millipore | Cat# 06–570; RRID: AB_310177 |
| Rabbit polyclonal anti-ATM | Bethyl Laboratories | Cat# A300-136A; RRID: AB_155872 |
| Rabbit monoclonal anti-ATR (E1S3S) | Cell Signaling Technology | Cat# 13934; RRID: AB_2798347 |
| Mouse monoclonal anti-CHK1 | Cell Signaling Technology | Cat# 2360; RRID: AB_2080320 |
| Rabbit monoclonal anti- phospho CHK1 (Ser345) | Cell Signaling Technology | Cat# 2348; RRID: AB_331212 |
| Rabbit monoclonal anti-βTRCP (D13F10) | Cell Signaling Technology | Cat# 4394; RRID: AB_10545763 |
| Mouse monoclonal anti-β-Actin | Sigma | Cat# A1978; RRID: AB_476692 |
| Rabbit monoclonal anti-phospho EGFR (Y1068) | Cell Signaling Technology | Cat# 3777; RRID: AB_2798512 |
| Rabbit monoclonal anti-EGFR(L858R mutant specific) (43B2) | Cell Signaling Technology | Cat# 3197; RRID: AB_1903955 |
| Rabbit monoclonal anti-phospho H2A.X | Cell Signaling Technology | Cat# 9718; RRID: AB_2118009 |
| Mouse monoclonal anti-alpha-tubulin (DM1A) | Sigma | Cat# T9026; RRID: AB_477593 |
| Mouse monoclonal anti-HA (12CA5) | Kim et al., 2006 | N/A |
| Biological Samples | ||
| ECLC26 patient-derived xenograft model | This paper | N/A |
| Ru813c patient-derived xenograft model | Dr. Charles Rudin (MSKCC) | N/A |
| Lx1114 patient-derived xenograft model | Dr. Charles Rudin (MSKCC) | N/A |
| Chemicals, Peptides, and Recombinant proteins | ||
| HTS chemical library | Selleck Chemicals | Table S6 |
| Osimertinib | Selleck Chemicals | Cat# S7297 |
| PF03814735 | Selleck Chemicals | Cat# S2725 |
| Rociletinib | Selleck Chemicals | Cat# S7284 |
| MLN8054 | Selleck Chemicals | Cat# S1100 |
| MLN8237 | Selleck Chemicals | Cat# S1133 |
| AZD1152 | Selleck Chemicals | Cat# S1147 |
| CCT137690 | Selleck Chemicals | Cat# S2744 |
| MK5108 | Selleck Chemicals | Cat# S2770 |
| Hesperadin | Selleck Chemicals | Cat# S1529 |
| GSK1070916 | Selleck Chemicals | Cat# S2740 |
| GSK1838705A | Selleck Chemicals | Cat# S2703 |
| NVP-AEW541 | Selleck Chemicals | Cat# S1034 |
| Rebastinib | Selleck Chemicals | Cat# S2634 |
| Saracatinib | Selleck Chemicals | Cat# S1006 |
| GDC0941 | Selleck Chemicals | Cat# S1065 |
| MK2206 | Selleck Chemicals | Cat# S1078 |
| Rapamycin | Selleck Chemicals | Cat# S1039 |
| CDK4/6 inhibitor (Palbociclib) | Selleck Chemicals | Cat# S1116 |
| CHK1 inhibitor (LY2603618) | Selleck Chemicals | Cat# S2626 |
| ATR inhibitor (VX-970) | Selleck Chemicals | Cat# S7102 |
| Nocodazole | Selleck Chemicals | Cat# S2775 |
| Trametinib | Selleck Chemicals | Cat# S2673 |
| Emetine | EMD Millipore | Cat# 324693 |
| Recombinant human AURKB protein | Thermo Fisher Scientific | Cat# PV6130 |
| Recombinant human AURKA protein | Thermo Fisher Scientific | Cat# PV3612 |
| Critical commercial assays | ||
| CellTiter-Glo Luminescent Cell Viability Assay | Promega | Cat# G7572 |
| alamarBlue Viability Assay | Thermo Fisher Scientific | DAL1100 |
| Annexin V-FITC | BioVision | Cat# 1001–1000 |
| Annexin V-Cy3 | BioVision | Cat# 1002–1000 |
| Deposited Data | ||
| RNA-seq | This paper | https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA736433 |
| Experimental Models: Cell lines | ||
| H1975: human EGFR-mutant NSCLC | ATCC | ATCC Cat# CRL-5908; RRID: CVCL_1511 |
| HCC827: human EGFR-mutant NSCLC | ATCC | ATCC Cat# CRL-2868; RRID: CVCL_2063 |
| PC9: human EGFR-mutant NSCLC | Dr. David Scheinberg (MSKCC) | RRID: CVCL_B260 |
| ECLC26: human EGFR-mutant NSCLC | This paper | N/A |
| 293T | ATCC | ATCC Cat# CRL-11268; RRID: CVCL_1926 |
| NIH3T3 | ATCC | ATCC Cat# CRL-1658; RRID: CVCL_0594 |
| Experimental Models: Organisms/Strains | ||
| Mouse: Athymic nude: NU(NCr)-Foxn1nu | Charles River Laboratories | CR: 490 |
| Mouse: NSG: NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ | The Jackson Laboratory | JAX: 005557 |
| Oligonucleotides | ||
| qRT-PCR: BIM | 5′-CCAGCACCCATGAGTTGTGACAA-3′ | |
| qRT-PCR: BIM | 5′-GCGTTAAACTCGTCTCCAATACGCC-3′ | |
| qRT-PCR: PUMA | 5′-ACGACCTCAACGCACAGTACG-3′ | |
| qRT-PCR: PUMA | 5′-GTAAGGGCAGGAGTCCCATGATG-3′ | |
| qRT-PCR: ACTB | 5′-TCCCTGGAGAAGAGCTACGAG-3′ | |
| qRT-PCR: ACTB | 5′-AGGAAGGAAGGCTGGAAGAGTG-3′ | |
| siRNA: AURKA | 5’-GAGUCUACCUAAUUCUGGAtt-3’ | Ambion Silencer Select Cat# s196 |
| siRNA: AURKA | 5’-ACAUACCAAGAGACCUACAtt-3’ | Ambion Silencer Select custom synthesis |
| siRNA: AURKB | 5’-CCUGCGUCUCUACAACUAUtt-3’ | Ambion Silencer Select Cat# s17611 |
| siRNA: AURKB | 5’-UCGUCAAGGUGGACCUAAAtt-3’ | Ambion Silencer Select Cat# s17612 |
| siRNA: BIM | 5’-CAACCACUAUCUCAGUGCAtt-3′ | Ambion Silencer Select Cat# s223065 |
| siRNA: PUMA | 5’-GCCUGUAAGAUACUGUAUAtt-3’ | Ambion Silencer Select Cat# s25840 |
| sgRNA: BAX | CAAGCGCATCGGGGACGAAC | |
| sgRNA: BAK | ACGGCAGCTCGCCATCATCG | |
| sgRNA: FOXA1 | CGCAGTAGCCGGCATGCCGG | |
| sgRNA: FOXA2 | ATGAACATGTCGTCGTACGT | |
| sgRNA: BIM | GCCCAAGAGTTGCGGCGTAT | |
| sgRNA: LacZ | TGCGAATACGCCCACGCGAT | |
| Recombinant DNA | ||
| MSCV-Hygro | Takara Bio | Cat# 634401 |
| lentiCRISPR_v2 vector | Addgene | Cat# 49535 |
| pBABE-Puro | Addgene | Cat# 1764 |
| MSCV-Hygro-N-Flag-HA-BIM | This paper | N/A |
| MSCV-Hygro-N-Flag-HA-BIM_S87A | This paper | N/A |
| MSCV-Hygro-N-Flag-HA-ZEB1 | This paper | N/A |
| pBABE-Puro-EGFR | This paper | N/A |
| pBABE-Puro-EGFR_L858R | This paper | N/A |
| pBABE-Puro-EGFR_P919T | This paper | N/A |
| pBABE-Puro-EGFR_L858R/P919T | This paper | N/A |
| Software and Algorithms | ||
| Graphpad Prism 8 | GraphPad | http://www.graphpad.com/scientific-software/prism/ |
| FlowJo | FlowJo LLC | www.flowjo.com |
| ImageJ software | ImageJ open source | http://imagej.net/Welcome |
| Trimmomatic | (Bolger et al., 2014) | http://www.usadellab.org/cms/?page=trimmomatic |
| STAR | (Dobin et al., 2013) | https://github.com/alexdobin/STAR |
| HTSeq | (Anders et al., 2015) | https://htseq.readthedocs.io/en/master/ |
| DESeq2 | (Love et al., 2014) | https://bioconductor.org/packages/release/bioc/html/DESeq2.html |
| GSEA | (Subramanian et al., 2005) | http://software.broadinstitute.org/gsea/index.jsp |
| Optimized CRISPR Design | CRISPR Design Tool MIT | https://zlab.bio/guide-design-resources |