Reagents or Tools	Source	Identifier
Antibodies
Rabbit Polyclonal Anti‐ACAT1 (WB)	Sigma	Cat# AV54278, RRID: AB_1844483
Mouse Monoclonal Anti‐ALCAM/CD166 (WB)	Santa Cruz Biotechnolgy	Cat# sc‐74558, RRID : AB_2289495
Mouse Monoclonal Anti‐ALCAM/CD166 (FACS)	BD Biosciences	Cat# 559260, RRID:AB_397209
Mouse Monoclonal Anti‐β‐Actin	Sigma‐Aldrich	Cat# A5316, RRID:AB_476743
Rabbit Polyclonal Anti‐BCAT1	Aviva Systems Biology	Cat# ARP46132_P050, RRID:AB_10640125
Rabbit Polyclonal Anti‐BDH1	Novus Biologicals	Cat# NBP1‐88673, RRID:AB_11009202
Rabbit Polyclonal Anti‐BDH2	Sigma	Cat# HPA036028, RRID:AB_10670674
Rabbit Polyclonal Anti‐Hmgcl	Abcam	Cat# ab197022, RRID:AB_2797140
Rabbit Polyclonal Anti‐Hmgcll1	Abcam	Cat# ab101576, RRID:AB_10712203
Rabbit monoclonal Anti‐HMGCS2 (IHC)	Abcam	Cat# ab137043, RRID: AB_2749817
Rabbit Polyclonal Anti‐HMGCS2 (WB)	Sigma	Cat# AV41562, RRID: AB_1850800
Rat Monoclonal Anti‐Ki67	Biolegend	Cat# 652402, RRID:AB_11204254
Rabbit Polyclonal Anti‐SLC16A7/MCT2	Bioss	Cat# bs‐3995R, RRID:AB_10855300
Rabbit Polyclonal Anti‐OXCT1 (SCOT1)	Novus Biologicals	Cat# NBP1‐82462, RRID:AB_11027140
Rabbit Polyclonal Anti‐OXCT2 (SCOT2)	Thermo Fisher Scientific	Cat# PA5‐49312, RRID:AB_2634766
Rat Polyclonal Human/Mouse anti‐Semaphorin 3C	R&D Systems	Cat# MAB1728, RRID:AB_2301533
Rabbit Polyclonal Anti‐SQLE	Proteintech	Cat# 12544‐1‐AP, RRID:AB_2195888
Rabbit Polyclonal Anti‐SLC5A8/SMCT1	Bioss	Cat# bs‐6106R, RRID:AB_11108966
Goat Polyclonal Anti‐Rat IgG ‐ HRP	Santa Cruz Biotechnolgy	Cat# sc‐2006, RRID:AB_1125219
Goat Polyclonal Anti‐Mouse IgG Human ads ‐ HRP	Southern Biotechnolgy	Cat# 1030‐05, RRID:AB_2619742
Goat Polyclonal Anti‐Rabbit IgG – HRP	Southern Biotechnolgy	Cat# 4030‐05, RRID:AB_2687483
Rabbit Polyclonal Anti‐Goat IgG (H + L) – HRP	Southern Biotechnolgy	Cat# 6160‐05, RRID:AB_2796231
Goat Polyclonal Anti‐Mouse IgG (H + L) ‐ Alexa Fluor 488	Thermo Fisher Scientific	Cat# A‐11029, RRID:AB_138404
Biological Samples
Healthy pancreas and PDA protein extract from PDA patients	Leca et al (2016)	https://doi.org/10.1172/JCI87734
Chemicals, Peptides, and Recombinant Proteins
Lipofectamine 3000	Thermo Fisher Scientific	Cat# L3000015
G418	Thermo Fisher Scientific	Cat# 10131027
Mitomycin C	Sigma Aldrich	Cat# 10107409001
Collagenase type V	Sigma Aldrich	Cat# C9263
Critical Commercial Assays
CellTrace™ CFSE Cell Proliferation Kit	Thermo Fisher Scientific	Cat# C34554
VECTASTAIN ABC kit	Vector	Cat# PK‐6100
Liquid DAB and substrate chromogen system	DAKO	Cat# K3468
Corning BioCoat™ Matrigel Invasion Chamber	Corning	Cat# 11553570
Trichrome Masson kit	RAL DIAGNOSTICS	Cat# 361350‐0000
Deposited Data
9‐week RMA data	Guillaumond et al (2015)	GSE61412
6‐week RMA data		GSE127891
Experimental Models: Cell Lines
PK4a mouse cells	Guillaumond et al (2013)	RRID:CVCL_WB21
PANC‐1 human cells	ATCC	Cat# CRL‐1469, RRID:CVCL_0480
MiaPaCa‐2 human cells	ATCC	Cat# CRL‐1420 RRID:CVCL_0428
Experimental Models: Organisms/Strains
Pdx1‐Cre; Ink4a/Arffl/fl;LSL‐KrasG12Dmice	Aguirre et al (2003)	https://doi.org/10.1101/gad.1158703
HsdCpb:NMRI‐Foxn1nu	Envigo	Cat# 5652667, RRID:MGI:5652667
Oligonucleotides
36B4 primer Forward AATCCCTGACGCACCGCCGTGATG	Guillaumond et al (2015)	https://doi.org/10.1073/pnas.1421601112
36B4 primer Reverse TGGGTTGTTTTCCAGGTGCCCTCG	Guillaumond et al (2015)	https://doi.org/10.1073/pnas.1421601112
Filamin B primer Forward AGTTAACCAGCCAGCATCCT	Devis et al (2017)	https://doi.org/10.1002/path.4851
Filamin B primer Reverse TGACATCGATGGTGTGGACA	Devis et al (2017)	https://doi.org/10.1002/path.4851
Epha2 primer Forward GGCTTCTTTATCCACCGCAG	Devis et al (2017)	https://doi.org/10.1002/path.4851
Epha2 primer Reverse CGAGGATGTCTTCAGCATGC	Devis et al (2017)	https://doi.org/10.1002/path.4851
Plau primer Forward TTCACCACCATCGAGAACCA	Devis et al (2017)	https://doi.org/10.1002/path.4851
Plau primer Reverse TTGCGTGTTGGAGTTAAGCC	Devis et al (2017)	https://doi.org/10.1002/path.4851
Recombinant DNA
HMGCL Crispr/Cas9 KO plasmids	Santa Cruz Biotechnologies	Cat# sc‐422425
HMGCL HDR plasmids	Santa Cruz Biotechnologies	Cat# sc‐403841‐HDR
Control CRISPR/Cas9Plasmid	Santa Cruz Biotechnologies	Cat# sc‐418922
pcDNA3.1(+)‐N‐DYK	GeneScript	/
ALCAM cDNA (pcDNA3.1(+)‐N‐DYK)	GeneScript	/
SQLE cDNA (pcDNA3.1(+)‐N‐DYK)	GeneScript	/
Software and Algorithms
R studio 3.4.4	RStudio, Inc.	RRID:SCR_000432
Gene Set Enrichment Analysis with the fgsea package	Bioconductor	RRID:SCR_003199
Image J	National Institutes of Health	RRID:SCR_003070
Prism Version 5.03	Graph Pad	RRID:SCR_002798
Ingenuity Pathway Analysis	IPA®	RRID:SCR_008653
FlowJo Version 10	FlowJo LLC	RRID:SCR_008520
Other
DMEM medium without glutamine (Gln‐)	Thermo Fisher Scientific	Cat# 11960‐044
DMEM medium without glutamine nor branched chain amino acid (BCAA‐)	Thermo Fisher Scientific	Cat# ME15212L1
DMEM medium without glutamine nor glucose (Glc‐)	Thermo Fisher Scientific	Cat# A14430‐01
Filtered foetal bovine serum	Hyclone	Cat# SH30070.02
Dialyzed foetal bovine serum	Hyclone	Cat# SH30079.02
Foetal bovine serum	BioSera	Cat# FB‐1280
Antibiotic/antimycotic solution	Thermo Fisher Scientific	Cat# 15240062
Leucine	Sigma Aldrich	Cat# L8912
Isoleucine	Sigma Aldrich	Cat# I7403
Valine	Sigma Aldrich	Cat# V0513
Sodium 3‐hydroxybutyrate	Sigma Aldrich	Cat# 54965
Acetoacetate	Sigma Aldrich	Cat# A8509
l‐Leucine (13C6)	Cambridge Isotope Laboratories	Cat# CLM‐2262‐H‐PK
Sodium D‐3‐Hydroxybutyrate (13C4)	Cambridge Isotope Laboratories	Cat# CLM‐3853‐PK
l‐glutamine (200 mM)	Thermo Fisher Scientific	Cat# 25030024
TransIT®‐LT1	Mirus	Cat# MIR2300