Chromatin Immunoprecipitation:
Article Title: The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer.
Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies ARNT Cell Signaling Tech Cat# 5537; RRID:AB_10694232 CBS Cell Signaling Tech. .. Cat# 14782; RRID:AB_2798609 COX IV Cell Signaling Tech Cat# 4850; RRID:AB_2085424 CTH ProteinTech Cat# 12217-1-AP; RRID:AB_2087497 Cytochrome c Cell Signaling Tech Cat# 4280; RRID:AB_10695410 FLAG Cell Signaling Tech Cat# 14793; AB_2572291 HIF-1α (for WB) BD Biosciences Cat# 610959; RRID:AB_398272 HIF-1α (for chIP) Novus Cat# NB100-479; RRID:AB_10000633 HIF-2α Invitrogen Cat# PA1-16510; RRID:AB_2098236 Parkin Cell Signaling Tech Cat# 2132; RRID:AB_10693040 PHB1 Cell Signaling Tech Cat# 2426; RRID:AB_823689 SDHA Cell Signaling Tech Cat# 11998; RRID:AB_2750900 SLC7A11 Cell Signaling Tech Cat# 12691; RRID:AB_2687474 SLC3A2 Cell Signaling Tech Cat# 47213; RRID:AB_2799323 β-tubulin Cell Signaling Tech Cat# 86298; RRID:AB_2715541 β-actin Cell Signaling Tech Cat# 4967; RRID:AB_330288 Chemicals, peptides, and recombinant proteins DFX Millipore Sigma Cat# 138-14-7 DMOG Cayman Chemicals Cat# 71210 Erastin Selleck Chemical Cat# S7242 Ferrostatin Med Chem Express Cat# SML0583 Imidazole Ketone Erastin Selleck Chem Cat# S8877 Roxadustat Cayman Chemicals Cat# 15294 RSL-3 Med Chem Express Cat# 15294 Sulfasalazine Med Chem Express Cat# HY-14655 Mitosox Red ThermoFisher Scientific Cat# M36008 Sybr Green PCR Master Mix ThermoFisher Scientific Cat# 4301955 Critical commercial assays Cell-Titer Glo Promega Cat# 7570 Lipid Peroxidation (4-HNE) Assay Kit Abcam Cat# ab238538 Dual Luciferase Assay Kit Promega Cat# E1910 Chromatin IP Kit Cell Signaling Tech Cat# 9003 RNeasy Mini Kit Qiagen Cat# 74104 iScript cDNA Synthesis system BioRad Cat# 1708890 PureLink Genomic DNA Mini Kit Invitrogen Cat# K182001 Deposited data RNA-seq data This paper GEO: GSE320200, GSE319951, GSE319526 Experimental models: Cell lines Human: PANC-1 ATCC Cat# CRL-1469 Human: PANC-1 VHL KO clone (CRISPR-Cas9); mCherry+ This paper N/A (Continued on next page) Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026 e1 .. REAGENT or RESOURCE SOURCE IDENTIFIER Human: PANC-1 HIF-1α KO Clone 1 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 2 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 3 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 3 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 Dox-Inducible shRNA-HIF-2α This paper N/A Human: PANC-1 Dox-Inducible HIF-1α (P402/564A) This paper N/A Human: PANC-1 Dox-Inducible HIF-2α (P402/564A) This paper N/A Human: PANC-1 Cas9+; GFP+ This paper N/A Human: PANC-1 Cas9+; mCherry+ This paper N/A Human: MiaPaCa HIF-1α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: AsPC-1 ATCC Cat# CRL-1682 Human: SW1990 ATCC Cat# CRL-2172 Human: CFPAC-1 ATCC Cat# CRL-1918 Human: BxPC-3 ATCC Cat# CRL-1687 Human: RCC4 Laboratory of Celeste Simon N/A Mouse: 6694 Laboratory of Ben Stanger48 N/A Experimental models: Organisms/strains Nod-Scid Gamma (NSG) Mice Johns Hopkins Animal Facility N/A Oligonucleotides All primers and sgRNAs used in this study (see Table S5) This paper Table S5 Recombinant DNA pCDH-EF1-FHC Addgene Cat# 64874 pCW57-MCS1-P2A-MCS2 Addgene Cat# 80921 psPAX2 Addgene Cat# 12260 pMD2.g Addgene Cat# 12259 LRG (lenti-sgRNA-EFS-GFP) Addgene Cat# 65656 LRG-sgRNA-HIF-2α-guide 1 - GFP This paper N/A LRG-sgRNA-HIF-2α-guide 2 – GFP This paper N/A LRG-sgRNA-HIF-2α-guide 3 – GFP This paper N/A LRG-sgRNA-ARNT-guide A – GFP This paper N/A (Continued on next page) e2 Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026
Western Blot:Article Title: The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer.
Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies ARNT Cell Signaling Tech Cat# 5537; RRID:AB_10694232 CBS Cell Signaling Tech. .. Cat# 14782; RRID:AB_2798609 COX IV Cell Signaling Tech Cat# 4850; RRID:AB_2085424 CTH ProteinTech Cat# 12217-1-AP; RRID:AB_2087497 Cytochrome c Cell Signaling Tech Cat# 4280; RRID:AB_10695410 FLAG Cell Signaling Tech Cat# 14793; AB_2572291 HIF-1α (for WB) BD Biosciences Cat# 610959; RRID:AB_398272 HIF-1α (for chIP) Novus Cat# NB100-479; RRID:AB_10000633 HIF-2α Invitrogen Cat# PA1-16510; RRID:AB_2098236 Parkin Cell Signaling Tech Cat# 2132; RRID:AB_10693040 PHB1 Cell Signaling Tech Cat# 2426; RRID:AB_823689 SDHA Cell Signaling Tech Cat# 11998; RRID:AB_2750900 SLC7A11 Cell Signaling Tech Cat# 12691; RRID:AB_2687474 SLC3A2 Cell Signaling Tech Cat# 47213; RRID:AB_2799323 β-tubulin Cell Signaling Tech Cat# 86298; RRID:AB_2715541 β-actin Cell Signaling Tech Cat# 4967; RRID:AB_330288 Chemicals, peptides, and recombinant proteins DFX Millipore Sigma Cat# 138-14-7 DMOG Cayman Chemicals Cat# 71210 Erastin Selleck Chemical Cat# S7242 Ferrostatin Med Chem Express Cat# SML0583 Imidazole Ketone Erastin Selleck Chem Cat# S8877 Roxadustat Cayman Chemicals Cat# 15294 RSL-3 Med Chem Express Cat# 15294 Sulfasalazine Med Chem Express Cat# HY-14655 Mitosox Red ThermoFisher Scientific Cat# M36008 Sybr Green PCR Master Mix ThermoFisher Scientific Cat# 4301955 Critical commercial assays Cell-Titer Glo Promega Cat# 7570 Lipid Peroxidation (4-HNE) Assay Kit Abcam Cat# ab238538 Dual Luciferase Assay Kit Promega Cat# E1910 Chromatin IP Kit Cell Signaling Tech Cat# 9003 RNeasy Mini Kit Qiagen Cat# 74104 iScript cDNA Synthesis system BioRad Cat# 1708890 PureLink Genomic DNA Mini Kit Invitrogen Cat# K182001 Deposited data RNA-seq data This paper GEO: GSE320200, GSE319951, GSE319526 Experimental models: Cell lines Human: PANC-1 ATCC Cat# CRL-1469 Human: PANC-1 VHL KO clone (CRISPR-Cas9); mCherry+ This paper N/A (Continued on next page) Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026 e1 .. REAGENT or RESOURCE SOURCE IDENTIFIER Human: PANC-1 HIF-1α KO Clone 1 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 2 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 3 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 3 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 Dox-Inducible shRNA-HIF-2α This paper N/A Human: PANC-1 Dox-Inducible HIF-1α (P402/564A) This paper N/A Human: PANC-1 Dox-Inducible HIF-2α (P402/564A) This paper N/A Human: PANC-1 Cas9+; GFP+ This paper N/A Human: PANC-1 Cas9+; mCherry+ This paper N/A Human: MiaPaCa HIF-1α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: AsPC-1 ATCC Cat# CRL-1682 Human: SW1990 ATCC Cat# CRL-2172 Human: CFPAC-1 ATCC Cat# CRL-1918 Human: BxPC-3 ATCC Cat# CRL-1687 Human: RCC4 Laboratory of Celeste Simon N/A Mouse: 6694 Laboratory of Ben Stanger48 N/A Experimental models: Organisms/strains Nod-Scid Gamma (NSG) Mice Johns Hopkins Animal Facility N/A Oligonucleotides All primers and sgRNAs used in this study (see Table S5) This paper Table S5 Recombinant DNA pCDH-EF1-FHC Addgene Cat# 64874 pCW57-MCS1-P2A-MCS2 Addgene Cat# 80921 psPAX2 Addgene Cat# 12260 pMD2.g Addgene Cat# 12259 LRG (lenti-sgRNA-EFS-GFP) Addgene Cat# 65656 LRG-sgRNA-HIF-2α-guide 1 - GFP This paper N/A LRG-sgRNA-HIF-2α-guide 2 – GFP This paper N/A LRG-sgRNA-HIF-2α-guide 3 – GFP This paper N/A LRG-sgRNA-ARNT-guide A – GFP This paper N/A (Continued on next page) e2 Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026
Recombinant:Article Title: The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer.
Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies ARNT Cell Signaling Tech Cat# 5537; RRID:AB_10694232 CBS Cell Signaling Tech. .. Cat# 14782; RRID:AB_2798609 COX IV Cell Signaling Tech Cat# 4850; RRID:AB_2085424 CTH ProteinTech Cat# 12217-1-AP; RRID:AB_2087497 Cytochrome c Cell Signaling Tech Cat# 4280; RRID:AB_10695410 FLAG Cell Signaling Tech Cat# 14793; AB_2572291 HIF-1α (for WB) BD Biosciences Cat# 610959; RRID:AB_398272 HIF-1α (for chIP) Novus Cat# NB100-479; RRID:AB_10000633 HIF-2α Invitrogen Cat# PA1-16510; RRID:AB_2098236 Parkin Cell Signaling Tech Cat# 2132; RRID:AB_10693040 PHB1 Cell Signaling Tech Cat# 2426; RRID:AB_823689 SDHA Cell Signaling Tech Cat# 11998; RRID:AB_2750900 SLC7A11 Cell Signaling Tech Cat# 12691; RRID:AB_2687474 SLC3A2 Cell Signaling Tech Cat# 47213; RRID:AB_2799323 β-tubulin Cell Signaling Tech Cat# 86298; RRID:AB_2715541 β-actin Cell Signaling Tech Cat# 4967; RRID:AB_330288 Chemicals, peptides, and recombinant proteins DFX Millipore Sigma Cat# 138-14-7 DMOG Cayman Chemicals Cat# 71210 Erastin Selleck Chemical Cat# S7242 Ferrostatin Med Chem Express Cat# SML0583 Imidazole Ketone Erastin Selleck Chem Cat# S8877 Roxadustat Cayman Chemicals Cat# 15294 RSL-3 Med Chem Express Cat# 15294 Sulfasalazine Med Chem Express Cat# HY-14655 Mitosox Red ThermoFisher Scientific Cat# M36008 Sybr Green PCR Master Mix ThermoFisher Scientific Cat# 4301955 Critical commercial assays Cell-Titer Glo Promega Cat# 7570 Lipid Peroxidation (4-HNE) Assay Kit Abcam Cat# ab238538 Dual Luciferase Assay Kit Promega Cat# E1910 Chromatin IP Kit Cell Signaling Tech Cat# 9003 RNeasy Mini Kit Qiagen Cat# 74104 iScript cDNA Synthesis system BioRad Cat# 1708890 PureLink Genomic DNA Mini Kit Invitrogen Cat# K182001 Deposited data RNA-seq data This paper GEO: GSE320200, GSE319951, GSE319526 Experimental models: Cell lines Human: PANC-1 ATCC Cat# CRL-1469 Human: PANC-1 VHL KO clone (CRISPR-Cas9); mCherry+ This paper N/A (Continued on next page) Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026 e1 .. REAGENT or RESOURCE SOURCE IDENTIFIER Human: PANC-1 HIF-1α KO Clone 1 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 2 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 3 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 3 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 Dox-Inducible shRNA-HIF-2α This paper N/A Human: PANC-1 Dox-Inducible HIF-1α (P402/564A) This paper N/A Human: PANC-1 Dox-Inducible HIF-2α (P402/564A) This paper N/A Human: PANC-1 Cas9+; GFP+ This paper N/A Human: PANC-1 Cas9+; mCherry+ This paper N/A Human: MiaPaCa HIF-1α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: AsPC-1 ATCC Cat# CRL-1682 Human: SW1990 ATCC Cat# CRL-2172 Human: CFPAC-1 ATCC Cat# CRL-1918 Human: BxPC-3 ATCC Cat# CRL-1687 Human: RCC4 Laboratory of Celeste Simon N/A Mouse: 6694 Laboratory of Ben Stanger48 N/A Experimental models: Organisms/strains Nod-Scid Gamma (NSG) Mice Johns Hopkins Animal Facility N/A Oligonucleotides All primers and sgRNAs used in this study (see Table S5) This paper Table S5 Recombinant DNA pCDH-EF1-FHC Addgene Cat# 64874 pCW57-MCS1-P2A-MCS2 Addgene Cat# 80921 psPAX2 Addgene Cat# 12260 pMD2.g Addgene Cat# 12259 LRG (lenti-sgRNA-EFS-GFP) Addgene Cat# 65656 LRG-sgRNA-HIF-2α-guide 1 - GFP This paper N/A LRG-sgRNA-HIF-2α-guide 2 – GFP This paper N/A LRG-sgRNA-HIF-2α-guide 3 – GFP This paper N/A LRG-sgRNA-ARNT-guide A – GFP This paper N/A (Continued on next page) e2 Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026
Article Title: MRE11 proximal polyadenylation site-mediated looping impacts transcription and genomic stability.
Article Snippet: In brief Huang et al. demonstrate that a proximal polyadenylation site in MRE11 forms a promoter-PAS loop that supports RNA polymerase recycling and transcription.. Disruption reduces MRN expression, impairs checkpoint function, and induces aberrant DNA replication, revealing PASmediated chromatin looping as a mechanism linking transcriptional regulation to genome stability.. Wild-type MRE11pPAS Deletion
SYBR Green Assay:Article Title: The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer.
Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies ARNT Cell Signaling Tech Cat# 5537; RRID:AB_10694232 CBS Cell Signaling Tech. .. Cat# 14782; RRID:AB_2798609 COX IV Cell Signaling Tech Cat# 4850; RRID:AB_2085424 CTH ProteinTech Cat# 12217-1-AP; RRID:AB_2087497 Cytochrome c Cell Signaling Tech Cat# 4280; RRID:AB_10695410 FLAG Cell Signaling Tech Cat# 14793; AB_2572291 HIF-1α (for WB) BD Biosciences Cat# 610959; RRID:AB_398272 HIF-1α (for chIP) Novus Cat# NB100-479; RRID:AB_10000633 HIF-2α Invitrogen Cat# PA1-16510; RRID:AB_2098236 Parkin Cell Signaling Tech Cat# 2132; RRID:AB_10693040 PHB1 Cell Signaling Tech Cat# 2426; RRID:AB_823689 SDHA Cell Signaling Tech Cat# 11998; RRID:AB_2750900 SLC7A11 Cell Signaling Tech Cat# 12691; RRID:AB_2687474 SLC3A2 Cell Signaling Tech Cat# 47213; RRID:AB_2799323 β-tubulin Cell Signaling Tech Cat# 86298; RRID:AB_2715541 β-actin Cell Signaling Tech Cat# 4967; RRID:AB_330288 Chemicals, peptides, and recombinant proteins DFX Millipore Sigma Cat# 138-14-7 DMOG Cayman Chemicals Cat# 71210 Erastin Selleck Chemical Cat# S7242 Ferrostatin Med Chem Express Cat# SML0583 Imidazole Ketone Erastin Selleck Chem Cat# S8877 Roxadustat Cayman Chemicals Cat# 15294 RSL-3 Med Chem Express Cat# 15294 Sulfasalazine Med Chem Express Cat# HY-14655 Mitosox Red ThermoFisher Scientific Cat# M36008 Sybr Green PCR Master Mix ThermoFisher Scientific Cat# 4301955 Critical commercial assays Cell-Titer Glo Promega Cat# 7570 Lipid Peroxidation (4-HNE) Assay Kit Abcam Cat# ab238538 Dual Luciferase Assay Kit Promega Cat# E1910 Chromatin IP Kit Cell Signaling Tech Cat# 9003 RNeasy Mini Kit Qiagen Cat# 74104 iScript cDNA Synthesis system BioRad Cat# 1708890 PureLink Genomic DNA Mini Kit Invitrogen Cat# K182001 Deposited data RNA-seq data This paper GEO: GSE320200, GSE319951, GSE319526 Experimental models: Cell lines Human: PANC-1 ATCC Cat# CRL-1469 Human: PANC-1 VHL KO clone (CRISPR-Cas9); mCherry+ This paper N/A (Continued on next page) Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026 e1 .. REAGENT or RESOURCE SOURCE IDENTIFIER Human: PANC-1 HIF-1α KO Clone 1 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 2 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 3 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 3 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 Dox-Inducible shRNA-HIF-2α This paper N/A Human: PANC-1 Dox-Inducible HIF-1α (P402/564A) This paper N/A Human: PANC-1 Dox-Inducible HIF-2α (P402/564A) This paper N/A Human: PANC-1 Cas9+; GFP+ This paper N/A Human: PANC-1 Cas9+; mCherry+ This paper N/A Human: MiaPaCa HIF-1α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: AsPC-1 ATCC Cat# CRL-1682 Human: SW1990 ATCC Cat# CRL-2172 Human: CFPAC-1 ATCC Cat# CRL-1918 Human: BxPC-3 ATCC Cat# CRL-1687 Human: RCC4 Laboratory of Celeste Simon N/A Mouse: 6694 Laboratory of Ben Stanger48 N/A Experimental models: Organisms/strains Nod-Scid Gamma (NSG) Mice Johns Hopkins Animal Facility N/A Oligonucleotides All primers and sgRNAs used in this study (see Table S5) This paper Table S5 Recombinant DNA pCDH-EF1-FHC Addgene Cat# 64874 pCW57-MCS1-P2A-MCS2 Addgene Cat# 80921 psPAX2 Addgene Cat# 12260 pMD2.g Addgene Cat# 12259 LRG (lenti-sgRNA-EFS-GFP) Addgene Cat# 65656 LRG-sgRNA-HIF-2α-guide 1 - GFP This paper N/A LRG-sgRNA-HIF-2α-guide 2 – GFP This paper N/A LRG-sgRNA-HIF-2α-guide 3 – GFP This paper N/A LRG-sgRNA-ARNT-guide A – GFP This paper N/A (Continued on next page) e2 Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026
Polymerase Chain Reaction:Article Title: The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer.
Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies ARNT Cell Signaling Tech Cat# 5537; RRID:AB_10694232 CBS Cell Signaling Tech. .. Cat# 14782; RRID:AB_2798609 COX IV Cell Signaling Tech Cat# 4850; RRID:AB_2085424 CTH ProteinTech Cat# 12217-1-AP; RRID:AB_2087497 Cytochrome c Cell Signaling Tech Cat# 4280; RRID:AB_10695410 FLAG Cell Signaling Tech Cat# 14793; AB_2572291 HIF-1α (for WB) BD Biosciences Cat# 610959; RRID:AB_398272 HIF-1α (for chIP) Novus Cat# NB100-479; RRID:AB_10000633 HIF-2α Invitrogen Cat# PA1-16510; RRID:AB_2098236 Parkin Cell Signaling Tech Cat# 2132; RRID:AB_10693040 PHB1 Cell Signaling Tech Cat# 2426; RRID:AB_823689 SDHA Cell Signaling Tech Cat# 11998; RRID:AB_2750900 SLC7A11 Cell Signaling Tech Cat# 12691; RRID:AB_2687474 SLC3A2 Cell Signaling Tech Cat# 47213; RRID:AB_2799323 β-tubulin Cell Signaling Tech Cat# 86298; RRID:AB_2715541 β-actin Cell Signaling Tech Cat# 4967; RRID:AB_330288 Chemicals, peptides, and recombinant proteins DFX Millipore Sigma Cat# 138-14-7 DMOG Cayman Chemicals Cat# 71210 Erastin Selleck Chemical Cat# S7242 Ferrostatin Med Chem Express Cat# SML0583 Imidazole Ketone Erastin Selleck Chem Cat# S8877 Roxadustat Cayman Chemicals Cat# 15294 RSL-3 Med Chem Express Cat# 15294 Sulfasalazine Med Chem Express Cat# HY-14655 Mitosox Red ThermoFisher Scientific Cat# M36008 Sybr Green PCR Master Mix ThermoFisher Scientific Cat# 4301955 Critical commercial assays Cell-Titer Glo Promega Cat# 7570 Lipid Peroxidation (4-HNE) Assay Kit Abcam Cat# ab238538 Dual Luciferase Assay Kit Promega Cat# E1910 Chromatin IP Kit Cell Signaling Tech Cat# 9003 RNeasy Mini Kit Qiagen Cat# 74104 iScript cDNA Synthesis system BioRad Cat# 1708890 PureLink Genomic DNA Mini Kit Invitrogen Cat# K182001 Deposited data RNA-seq data This paper GEO: GSE320200, GSE319951, GSE319526 Experimental models: Cell lines Human: PANC-1 ATCC Cat# CRL-1469 Human: PANC-1 VHL KO clone (CRISPR-Cas9); mCherry+ This paper N/A (Continued on next page) Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026 e1 .. REAGENT or RESOURCE SOURCE IDENTIFIER Human: PANC-1 HIF-1α KO Clone 1 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 2 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 3 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 3 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 Dox-Inducible shRNA-HIF-2α This paper N/A Human: PANC-1 Dox-Inducible HIF-1α (P402/564A) This paper N/A Human: PANC-1 Dox-Inducible HIF-2α (P402/564A) This paper N/A Human: PANC-1 Cas9+; GFP+ This paper N/A Human: PANC-1 Cas9+; mCherry+ This paper N/A Human: MiaPaCa HIF-1α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: AsPC-1 ATCC Cat# CRL-1682 Human: SW1990 ATCC Cat# CRL-2172 Human: CFPAC-1 ATCC Cat# CRL-1918 Human: BxPC-3 ATCC Cat# CRL-1687 Human: RCC4 Laboratory of Celeste Simon N/A Mouse: 6694 Laboratory of Ben Stanger48 N/A Experimental models: Organisms/strains Nod-Scid Gamma (NSG) Mice Johns Hopkins Animal Facility N/A Oligonucleotides All primers and sgRNAs used in this study (see Table S5) This paper Table S5 Recombinant DNA pCDH-EF1-FHC Addgene Cat# 64874 pCW57-MCS1-P2A-MCS2 Addgene Cat# 80921 psPAX2 Addgene Cat# 12260 pMD2.g Addgene Cat# 12259 LRG (lenti-sgRNA-EFS-GFP) Addgene Cat# 65656 LRG-sgRNA-HIF-2α-guide 1 - GFP This paper N/A LRG-sgRNA-HIF-2α-guide 2 – GFP This paper N/A LRG-sgRNA-HIF-2α-guide 3 – GFP This paper N/A LRG-sgRNA-ARNT-guide A – GFP This paper N/A (Continued on next page) e2 Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026
Luciferase:Article Title: The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer.
Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies ARNT Cell Signaling Tech Cat# 5537; RRID:AB_10694232 CBS Cell Signaling Tech. .. Cat# 14782; RRID:AB_2798609 COX IV Cell Signaling Tech Cat# 4850; RRID:AB_2085424 CTH ProteinTech Cat# 12217-1-AP; RRID:AB_2087497 Cytochrome c Cell Signaling Tech Cat# 4280; RRID:AB_10695410 FLAG Cell Signaling Tech Cat# 14793; AB_2572291 HIF-1α (for WB) BD Biosciences Cat# 610959; RRID:AB_398272 HIF-1α (for chIP) Novus Cat# NB100-479; RRID:AB_10000633 HIF-2α Invitrogen Cat# PA1-16510; RRID:AB_2098236 Parkin Cell Signaling Tech Cat# 2132; RRID:AB_10693040 PHB1 Cell Signaling Tech Cat# 2426; RRID:AB_823689 SDHA Cell Signaling Tech Cat# 11998; RRID:AB_2750900 SLC7A11 Cell Signaling Tech Cat# 12691; RRID:AB_2687474 SLC3A2 Cell Signaling Tech Cat# 47213; RRID:AB_2799323 β-tubulin Cell Signaling Tech Cat# 86298; RRID:AB_2715541 β-actin Cell Signaling Tech Cat# 4967; RRID:AB_330288 Chemicals, peptides, and recombinant proteins DFX Millipore Sigma Cat# 138-14-7 DMOG Cayman Chemicals Cat# 71210 Erastin Selleck Chemical Cat# S7242 Ferrostatin Med Chem Express Cat# SML0583 Imidazole Ketone Erastin Selleck Chem Cat# S8877 Roxadustat Cayman Chemicals Cat# 15294 RSL-3 Med Chem Express Cat# 15294 Sulfasalazine Med Chem Express Cat# HY-14655 Mitosox Red ThermoFisher Scientific Cat# M36008 Sybr Green PCR Master Mix ThermoFisher Scientific Cat# 4301955 Critical commercial assays Cell-Titer Glo Promega Cat# 7570 Lipid Peroxidation (4-HNE) Assay Kit Abcam Cat# ab238538 Dual Luciferase Assay Kit Promega Cat# E1910 Chromatin IP Kit Cell Signaling Tech Cat# 9003 RNeasy Mini Kit Qiagen Cat# 74104 iScript cDNA Synthesis system BioRad Cat# 1708890 PureLink Genomic DNA Mini Kit Invitrogen Cat# K182001 Deposited data RNA-seq data This paper GEO: GSE320200, GSE319951, GSE319526 Experimental models: Cell lines Human: PANC-1 ATCC Cat# CRL-1469 Human: PANC-1 VHL KO clone (CRISPR-Cas9); mCherry+ This paper N/A (Continued on next page) Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026 e1 .. REAGENT or RESOURCE SOURCE IDENTIFIER Human: PANC-1 HIF-1α KO Clone 1 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 2 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 3 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 3 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 Dox-Inducible shRNA-HIF-2α This paper N/A Human: PANC-1 Dox-Inducible HIF-1α (P402/564A) This paper N/A Human: PANC-1 Dox-Inducible HIF-2α (P402/564A) This paper N/A Human: PANC-1 Cas9+; GFP+ This paper N/A Human: PANC-1 Cas9+; mCherry+ This paper N/A Human: MiaPaCa HIF-1α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: AsPC-1 ATCC Cat# CRL-1682 Human: SW1990 ATCC Cat# CRL-2172 Human: CFPAC-1 ATCC Cat# CRL-1918 Human: BxPC-3 ATCC Cat# CRL-1687 Human: RCC4 Laboratory of Celeste Simon N/A Mouse: 6694 Laboratory of Ben Stanger48 N/A Experimental models: Organisms/strains Nod-Scid Gamma (NSG) Mice Johns Hopkins Animal Facility N/A Oligonucleotides All primers and sgRNAs used in this study (see Table S5) This paper Table S5 Recombinant DNA pCDH-EF1-FHC Addgene Cat# 64874 pCW57-MCS1-P2A-MCS2 Addgene Cat# 80921 psPAX2 Addgene Cat# 12260 pMD2.g Addgene Cat# 12259 LRG (lenti-sgRNA-EFS-GFP) Addgene Cat# 65656 LRG-sgRNA-HIF-2α-guide 1 - GFP This paper N/A LRG-sgRNA-HIF-2α-guide 2 – GFP This paper N/A LRG-sgRNA-HIF-2α-guide 3 – GFP This paper N/A LRG-sgRNA-ARNT-guide A – GFP This paper N/A (Continued on next page) e2 Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026
cDNA Synthesis:Article Title: The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer.
Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies ARNT Cell Signaling Tech Cat# 5537; RRID:AB_10694232 CBS Cell Signaling Tech. .. Cat# 14782; RRID:AB_2798609 COX IV Cell Signaling Tech Cat# 4850; RRID:AB_2085424 CTH ProteinTech Cat# 12217-1-AP; RRID:AB_2087497 Cytochrome c Cell Signaling Tech Cat# 4280; RRID:AB_10695410 FLAG Cell Signaling Tech Cat# 14793; AB_2572291 HIF-1α (for WB) BD Biosciences Cat# 610959; RRID:AB_398272 HIF-1α (for chIP) Novus Cat# NB100-479; RRID:AB_10000633 HIF-2α Invitrogen Cat# PA1-16510; RRID:AB_2098236 Parkin Cell Signaling Tech Cat# 2132; RRID:AB_10693040 PHB1 Cell Signaling Tech Cat# 2426; RRID:AB_823689 SDHA Cell Signaling Tech Cat# 11998; RRID:AB_2750900 SLC7A11 Cell Signaling Tech Cat# 12691; RRID:AB_2687474 SLC3A2 Cell Signaling Tech Cat# 47213; RRID:AB_2799323 β-tubulin Cell Signaling Tech Cat# 86298; RRID:AB_2715541 β-actin Cell Signaling Tech Cat# 4967; RRID:AB_330288 Chemicals, peptides, and recombinant proteins DFX Millipore Sigma Cat# 138-14-7 DMOG Cayman Chemicals Cat# 71210 Erastin Selleck Chemical Cat# S7242 Ferrostatin Med Chem Express Cat# SML0583 Imidazole Ketone Erastin Selleck Chem Cat# S8877 Roxadustat Cayman Chemicals Cat# 15294 RSL-3 Med Chem Express Cat# 15294 Sulfasalazine Med Chem Express Cat# HY-14655 Mitosox Red ThermoFisher Scientific Cat# M36008 Sybr Green PCR Master Mix ThermoFisher Scientific Cat# 4301955 Critical commercial assays Cell-Titer Glo Promega Cat# 7570 Lipid Peroxidation (4-HNE) Assay Kit Abcam Cat# ab238538 Dual Luciferase Assay Kit Promega Cat# E1910 Chromatin IP Kit Cell Signaling Tech Cat# 9003 RNeasy Mini Kit Qiagen Cat# 74104 iScript cDNA Synthesis system BioRad Cat# 1708890 PureLink Genomic DNA Mini Kit Invitrogen Cat# K182001 Deposited data RNA-seq data This paper GEO: GSE320200, GSE319951, GSE319526 Experimental models: Cell lines Human: PANC-1 ATCC Cat# CRL-1469 Human: PANC-1 VHL KO clone (CRISPR-Cas9); mCherry+ This paper N/A (Continued on next page) Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026 e1 .. REAGENT or RESOURCE SOURCE IDENTIFIER Human: PANC-1 HIF-1α KO Clone 1 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 2 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 3 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 3 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 Dox-Inducible shRNA-HIF-2α This paper N/A Human: PANC-1 Dox-Inducible HIF-1α (P402/564A) This paper N/A Human: PANC-1 Dox-Inducible HIF-2α (P402/564A) This paper N/A Human: PANC-1 Cas9+; GFP+ This paper N/A Human: PANC-1 Cas9+; mCherry+ This paper N/A Human: MiaPaCa HIF-1α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: AsPC-1 ATCC Cat# CRL-1682 Human: SW1990 ATCC Cat# CRL-2172 Human: CFPAC-1 ATCC Cat# CRL-1918 Human: BxPC-3 ATCC Cat# CRL-1687 Human: RCC4 Laboratory of Celeste Simon N/A Mouse: 6694 Laboratory of Ben Stanger48 N/A Experimental models: Organisms/strains Nod-Scid Gamma (NSG) Mice Johns Hopkins Animal Facility N/A Oligonucleotides All primers and sgRNAs used in this study (see Table S5) This paper Table S5 Recombinant DNA pCDH-EF1-FHC Addgene Cat# 64874 pCW57-MCS1-P2A-MCS2 Addgene Cat# 80921 psPAX2 Addgene Cat# 12260 pMD2.g Addgene Cat# 12259 LRG (lenti-sgRNA-EFS-GFP) Addgene Cat# 65656 LRG-sgRNA-HIF-2α-guide 1 - GFP This paper N/A LRG-sgRNA-HIF-2α-guide 2 – GFP This paper N/A LRG-sgRNA-HIF-2α-guide 3 – GFP This paper N/A LRG-sgRNA-ARNT-guide A – GFP This paper N/A (Continued on next page) e2 Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026
RNA Sequencing:Article Title: The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer.
Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies ARNT Cell Signaling Tech Cat# 5537; RRID:AB_10694232 CBS Cell Signaling Tech. .. Cat# 14782; RRID:AB_2798609 COX IV Cell Signaling Tech Cat# 4850; RRID:AB_2085424 CTH ProteinTech Cat# 12217-1-AP; RRID:AB_2087497 Cytochrome c Cell Signaling Tech Cat# 4280; RRID:AB_10695410 FLAG Cell Signaling Tech Cat# 14793; AB_2572291 HIF-1α (for WB) BD Biosciences Cat# 610959; RRID:AB_398272 HIF-1α (for chIP) Novus Cat# NB100-479; RRID:AB_10000633 HIF-2α Invitrogen Cat# PA1-16510; RRID:AB_2098236 Parkin Cell Signaling Tech Cat# 2132; RRID:AB_10693040 PHB1 Cell Signaling Tech Cat# 2426; RRID:AB_823689 SDHA Cell Signaling Tech Cat# 11998; RRID:AB_2750900 SLC7A11 Cell Signaling Tech Cat# 12691; RRID:AB_2687474 SLC3A2 Cell Signaling Tech Cat# 47213; RRID:AB_2799323 β-tubulin Cell Signaling Tech Cat# 86298; RRID:AB_2715541 β-actin Cell Signaling Tech Cat# 4967; RRID:AB_330288 Chemicals, peptides, and recombinant proteins DFX Millipore Sigma Cat# 138-14-7 DMOG Cayman Chemicals Cat# 71210 Erastin Selleck Chemical Cat# S7242 Ferrostatin Med Chem Express Cat# SML0583 Imidazole Ketone Erastin Selleck Chem Cat# S8877 Roxadustat Cayman Chemicals Cat# 15294 RSL-3 Med Chem Express Cat# 15294 Sulfasalazine Med Chem Express Cat# HY-14655 Mitosox Red ThermoFisher Scientific Cat# M36008 Sybr Green PCR Master Mix ThermoFisher Scientific Cat# 4301955 Critical commercial assays Cell-Titer Glo Promega Cat# 7570 Lipid Peroxidation (4-HNE) Assay Kit Abcam Cat# ab238538 Dual Luciferase Assay Kit Promega Cat# E1910 Chromatin IP Kit Cell Signaling Tech Cat# 9003 RNeasy Mini Kit Qiagen Cat# 74104 iScript cDNA Synthesis system BioRad Cat# 1708890 PureLink Genomic DNA Mini Kit Invitrogen Cat# K182001 Deposited data RNA-seq data This paper GEO: GSE320200, GSE319951, GSE319526 Experimental models: Cell lines Human: PANC-1 ATCC Cat# CRL-1469 Human: PANC-1 VHL KO clone (CRISPR-Cas9); mCherry+ This paper N/A (Continued on next page) Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026 e1 .. REAGENT or RESOURCE SOURCE IDENTIFIER Human: PANC-1 HIF-1α KO Clone 1 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 2 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 3 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 3 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 Dox-Inducible shRNA-HIF-2α This paper N/A Human: PANC-1 Dox-Inducible HIF-1α (P402/564A) This paper N/A Human: PANC-1 Dox-Inducible HIF-2α (P402/564A) This paper N/A Human: PANC-1 Cas9+; GFP+ This paper N/A Human: PANC-1 Cas9+; mCherry+ This paper N/A Human: MiaPaCa HIF-1α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: AsPC-1 ATCC Cat# CRL-1682 Human: SW1990 ATCC Cat# CRL-2172 Human: CFPAC-1 ATCC Cat# CRL-1918 Human: BxPC-3 ATCC Cat# CRL-1687 Human: RCC4 Laboratory of Celeste Simon N/A Mouse: 6694 Laboratory of Ben Stanger48 N/A Experimental models: Organisms/strains Nod-Scid Gamma (NSG) Mice Johns Hopkins Animal Facility N/A Oligonucleotides All primers and sgRNAs used in this study (see Table S5) This paper Table S5 Recombinant DNA pCDH-EF1-FHC Addgene Cat# 64874 pCW57-MCS1-P2A-MCS2 Addgene Cat# 80921 psPAX2 Addgene Cat# 12260 pMD2.g Addgene Cat# 12259 LRG (lenti-sgRNA-EFS-GFP) Addgene Cat# 65656 LRG-sgRNA-HIF-2α-guide 1 - GFP This paper N/A LRG-sgRNA-HIF-2α-guide 2 – GFP This paper N/A LRG-sgRNA-HIF-2α-guide 3 – GFP This paper N/A LRG-sgRNA-ARNT-guide A – GFP This paper N/A (Continued on next page) e2 Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026
CRISPR:Article Title: The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer.
Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies ARNT Cell Signaling Tech Cat# 5537; RRID:AB_10694232 CBS Cell Signaling Tech. .. Cat# 14782; RRID:AB_2798609 COX IV Cell Signaling Tech Cat# 4850; RRID:AB_2085424 CTH ProteinTech Cat# 12217-1-AP; RRID:AB_2087497 Cytochrome c Cell Signaling Tech Cat# 4280; RRID:AB_10695410 FLAG Cell Signaling Tech Cat# 14793; AB_2572291 HIF-1α (for WB) BD Biosciences Cat# 610959; RRID:AB_398272 HIF-1α (for chIP) Novus Cat# NB100-479; RRID:AB_10000633 HIF-2α Invitrogen Cat# PA1-16510; RRID:AB_2098236 Parkin Cell Signaling Tech Cat# 2132; RRID:AB_10693040 PHB1 Cell Signaling Tech Cat# 2426; RRID:AB_823689 SDHA Cell Signaling Tech Cat# 11998; RRID:AB_2750900 SLC7A11 Cell Signaling Tech Cat# 12691; RRID:AB_2687474 SLC3A2 Cell Signaling Tech Cat# 47213; RRID:AB_2799323 β-tubulin Cell Signaling Tech Cat# 86298; RRID:AB_2715541 β-actin Cell Signaling Tech Cat# 4967; RRID:AB_330288 Chemicals, peptides, and recombinant proteins DFX Millipore Sigma Cat# 138-14-7 DMOG Cayman Chemicals Cat# 71210 Erastin Selleck Chemical Cat# S7242 Ferrostatin Med Chem Express Cat# SML0583 Imidazole Ketone Erastin Selleck Chem Cat# S8877 Roxadustat Cayman Chemicals Cat# 15294 RSL-3 Med Chem Express Cat# 15294 Sulfasalazine Med Chem Express Cat# HY-14655 Mitosox Red ThermoFisher Scientific Cat# M36008 Sybr Green PCR Master Mix ThermoFisher Scientific Cat# 4301955 Critical commercial assays Cell-Titer Glo Promega Cat# 7570 Lipid Peroxidation (4-HNE) Assay Kit Abcam Cat# ab238538 Dual Luciferase Assay Kit Promega Cat# E1910 Chromatin IP Kit Cell Signaling Tech Cat# 9003 RNeasy Mini Kit Qiagen Cat# 74104 iScript cDNA Synthesis system BioRad Cat# 1708890 PureLink Genomic DNA Mini Kit Invitrogen Cat# K182001 Deposited data RNA-seq data This paper GEO: GSE320200, GSE319951, GSE319526 Experimental models: Cell lines Human: PANC-1 ATCC Cat# CRL-1469 Human: PANC-1 VHL KO clone (CRISPR-Cas9); mCherry+ This paper N/A (Continued on next page) Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026 e1 .. REAGENT or RESOURCE SOURCE IDENTIFIER Human: PANC-1 HIF-1α KO Clone 1 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 2 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-1α KO Clone 3 (CRISPR- Cas9); mCherry+ This paper N/A Human: PANC-1 HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 HIF-2α KO Clone 3 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 ARNT KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: PANC-1 Dox-Inducible shRNA-HIF-2α This paper N/A Human: PANC-1 Dox-Inducible HIF-1α (P402/564A) This paper N/A Human: PANC-1 Dox-Inducible HIF-2α (P402/564A) This paper N/A Human: PANC-1 Cas9+; GFP+ This paper N/A Human: PANC-1 Cas9+; mCherry+ This paper N/A Human: MiaPaCa HIF-1α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 1 (CRISPR-Cas9); GFP+ This paper N/A Human: MiaPaCa HIF-2α KO Clone 2 (CRISPR-Cas9); GFP+ This paper N/A Human: AsPC-1 ATCC Cat# CRL-1682 Human: SW1990 ATCC Cat# CRL-2172 Human: CFPAC-1 ATCC Cat# CRL-1918 Human: BxPC-3 ATCC Cat# CRL-1687 Human: RCC4 Laboratory of Celeste Simon N/A Mouse: 6694 Laboratory of Ben Stanger48 N/A Experimental models: Organisms/strains Nod-Scid Gamma (NSG) Mice Johns Hopkins Animal Facility N/A Oligonucleotides All primers and sgRNAs used in this study (see Table S5) This paper Table S5 Recombinant DNA pCDH-EF1-FHC Addgene Cat# 64874 pCW57-MCS1-P2A-MCS2 Addgene Cat# 80921 psPAX2 Addgene Cat# 12260 pMD2.g Addgene Cat# 12259 LRG (lenti-sgRNA-EFS-GFP) Addgene Cat# 65656 LRG-sgRNA-HIF-2α-guide 1 - GFP This paper N/A LRG-sgRNA-HIF-2α-guide 2 – GFP This paper N/A LRG-sgRNA-HIF-2α-guide 3 – GFP This paper N/A LRG-sgRNA-ARNT-guide A – GFP This paper N/A (Continued on next page) e2 Molecular Cell 86, 1260–1274.e1–e4, April 2, 2026
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