REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit polyclonal anti-NIS	Proteintech	Cat# 24324-1-AP, RRID: AB_2879495
Rabbit polyclonal anti-VCP	Proteintech	Cat# 10736-1-AP, RRID: AB_2214635
Rabbit polyclonal anti-p62/SQSTM1	Proteintech	Cat# 18420-1-AP, RRID: AB_10694431
Rabbit polyclonal anti-LC3B	Cell Signalling Technology	Cat# 2775, RRID: AB_915950
Mouse monoclonal anti-HA	BioLegend	Cat# 901501, RRID: AB_2565006
Mouse monoclonal anti-β-actin	Sigma-Aldrich	Cat# A1978, RRID: AB_476692
Bacterial and Virus Strains
Subcloning Efficiency™ DH5α Competent Cells	ThermoFisher	Cat# 18265017
Biological Samples
Human thyroid tissue	Queen Elizabeth Hospital, Birmingham	N/A
Chemicals, Peptides, and Recombinant Proteins
Astemizole	Sigma-Aldrich	Cat# 2861
Carebastine	Sigma-Aldrich	Cat# 24186
CB-5083	Cayman Chemical	Cat# 19311
Chloroquine Diphosphate	Sigma-Aldrich	Cat# C6628
Clotrimazole	Sigma-Aldrich	Cat# C6019
DBeQ	Sigma-Aldrich	Cat# 506190
Dimethyl Sulfoxide	Sigma-Aldrich	Cat# D2650
Disulfiram	Sigma-Aldrich	Cat# 86720
Dynasore	Sigma-Aldrich	Cat# D9673
Ebastine	Sigma-Aldrich	Cat# E9531
Eeyarestatin-1	Cayman Chemicals	Cat# 10012609
Fexofenadine HCL	Sigma-Aldrich	Cat# F9427
Formoterol Hemifumarate	Stratech Scientific	Cat# B1359
Imatinib Mesylate	Cambridge Bioscience	Cat# 13139
Niflumic Acid	Alfa Aesar	Cat# J60489
NMS-873	SelleckChem	Cat# S7285
Phenformin HCL	Stratech Scientific	Cat# B1373
Phosphate Buffered Saline	ThermoFisher	Cat# 14190094
Pravastatin Sodium Salt	Cambridge Bioscience	Cat# 10010343
SAHA	Stratech Scientific	Cat# S1047
Selumetinib	SelleckChem	Cat# S1008
Sodium Iodide	Sigma-Aldrich	Cat# 383112
Sodium Perchlorate	Sigma-Aldrich	Cat# 410241
Sulconazole Nitrate	Sigma-Aldrich	Cat# 1623681
Terfenadine	Sigma-Aldrich	Cat# T9652
TRI Reagent	Sigma-Aldrich	Cat# 93289
Vatalanib 2HCL	Stratech Scientific	Cat# A1778
Vemurafenib	SelleckChem	Cat# S1267
Zimelidine 2HCL	Sigma-Aldrich	Cat# Z101
Critical Commercial Assays
Lipofectamine RNAiMAX	ThermoFisher Scientific	Cat# 13778075
RNeasy Micro Kit	Qiagen	Cat# 74004
Reverse Transcription System	Promega	Cat# A3500
EndoFree Plasmid Maxi Kit	Qiagen	Cat# 12362
TaqMan® Gene Expression Master Mix	Applied Biosystems	Cat# 10525395
Nano-Glo Live Cell Assay Solution	Promega	Cat# N2011
NIS TaqMan® Gene Expression Assay	ThermoFisher Scientific	Cat# Hs00166567_m1
PPIA TaqMan® Gene Expression Assay	ThermoFisher Scientific	Cat# Hs04194521_s1
VCP TaqMan® Gene Expression Assay	ThermoFisher Scientific	Cat# HS00997642_m1
Deposited data
The Connectivity Map (CMAP)	Subramanian et al., 2017	https://clue.io/touchstone
Data source file	This paper	Mendeley Data: https://doi.org/10.17632/vf3xnyxyp9.1
GSE27155	Giordano et al., 2005	https://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE27155
GSE76039	Landa et al., 2016	https://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE76039
TCGA GDAC Firehose standard data – Thyroid Carcinoma (THCA)	Broad Institute of MIT and Harvard	Firehose stddata__2016_01_28 run. https://doi.org/10.7908/C11G0KM9
TCGA THCA	Grossman et al., 2016	https://portal.gdc.cancer.gov/projects/TCGA-THCA
Thyroid carcinoma (TCGA, Firehose Legacy)	Cerami et al., 2012; Gao et al., 2013	https://www.cbioportal.org/study/summary?id=thca_tcga
Experimental Models: Cell Lines
TPC-1	Rebecca Schweppe’s lab	N/A
TPC-1-YFP	This paper	N/A
TPC-1-NIS-YFP	This paper	N/A
8505C	DSMZ	Cat# ACC-219, RRID:CVCL_1054
8505C-YFP	This paper	N/A
8505C-NIS-YFP	This paper	N/A
MDA-MB-231	ECACC	Cat# 92020424, RRID:CVCL_0062
MCF7	ECACC	Cat# 86012803, RRID:CVCL_0031
MDA-MB-231-NIS	Fletcher et al., 2020	N/A
HeLa	ECACC	Cat# 93021013, RRID:CVCL_0030
Oligonucleotides
MISSION VCP siRNA	Sigma-Aldrich	Cat# NM_007126
LgBiT (Forward)5’-GCCAAGCTTAC CATGGTCTTCACACTCGAA-3’	Sigma-Aldrich	Custom synthesis
LgBiT (Reverse)5’-GGCGGTACCAC TGTTGATGGTTA CTCG-3’	Sigma-Aldrich	Custom synthesis
VCP (Forward)5’-GCGGTACCGCTT CTGGAGCCGATTCA-3’	Sigma-Aldrich	Custom synthesis
VCP (Reverse)5’-GCCGCCTCTAG ATTAGCCATACAGGTCATC-3’	Sigma-Aldrich	Custom synthesis
NIS-SmBiT (Forward)5’-GCCGGTACC ACCATGGAGGCCGTGGAGACC-3’	Sigma-Aldrich	Custom synthesis
NIS-SmBiT (Reverse)5’-GCCTCTAGA TTACAGAATCTCCTCGAACAGCCGG TAGCCGGTCACGAGGTTTGTCTCC TGCTG-3’	Sigma-Aldrich	Custom synthesis
Recombinant DNA
pcDNA3.1-EYFP-H148Q/I152L/F46L	Alan Verkman’s lab	N/A
pcDNA3.1-NIS	Smith et al., 2009	N/A
Halo-tagSmBiT (negative control)	Caroline Gorvin’s lab	N/A
LgBiT-PRKAR2A (positive control)	Caroline Gorvin’s lab	N/A
SmBiT-PRKACA (positive control)	Caroline Gorvin’s lab	N/A
pcDNA3.1-LgBiT-VCP	This paper	N/A
pcDNA3.1-NIS-SmBiT	This paper	N/A
Software and Algorithms
GraphPad Prism Version 9	Graphpad Software Inc	https://www.graphpad.com/scientificsoftware/prism/
ImageJ	National Institutes of Health	https://imagej.nih.gov/ij/
IBM SPSS Statistics Version 27	IBM	https://www.ibm.com/uk-en/products/spss-statistics
BioRender	BioRender	https://biorender.com/
EC50 Calculator	AAT Bioquest	https://www.aatbio.com/tools/ec50-calculator
GEO2R	National Center for Biotechnology Information	https://www.ncbi.nlm.nih.gov/geo/geo2r/
DynaVenn	Chair for Clinical Bioinformatics at Saarland University	https://ccb-compute.cs.uni-saarland.de/dynavenn
Other
Prestwick Chemical Library	Birmingham Drug Discovery Facility	https://www.birmingham.ac.uk/facilities/bddf/compound-collections/index.aspx
Opera Phenix High-Content Screening System	Perkin Elmer	Cat# HH14000000
Microlab STAR Liquid Handling System	Hamilton	https://www.hamiltoncompany.com/automated-liquid-handling/platforms/microlab-star
PHERAstar FS microplate reader	BMG Labtech	https://www.bmglabtech.com/pherastar-fsx/
POLARstar Omega microplate reader	BMG Labtech	https://www.bmglabtech.com/polarstar-omega/
Multi Crystal LB 2111 Gamma Counter	Berthold	https://www.berthold.com/en/
7500 Real-Time PCR system	ThermoFisher Scientific	Cat# 4351105