REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit polyclonal anti-AChE	Proteintech	Cat# 17975-1-AP; RRID: AB_2242349
Rabbit polyclonal anti-CHRM4	Sigma-Aldrich	Cat# SAB4300824
Rabbit monoclonal anti-ChAT	Abcam	Cat# ab181023; RRID: AB_2687983
Rabbit polyclonal anti-CHRM1 (for IHC and PLA)	Sigma-Aldrich	Cat# HPA014101; RRID: AB_1854210
Rabbit polyclonal anti-CHRM1 (for immunoblots)	Abcam	Cat# ab180636
Rabbit polyclonal anti-cleaved caspase 3	Cell Signaling Technology	Cat# 9661; RRID: AB_2341188
Rabbit polyclonal anti-cleaved PARP1	Cell Signaling Technology	Cat# 9541; RRID: AB_331426
Mouse monoclonal anti-cMET (for PLA)	Cell Signaling Technology	Cat# 8741; RRID: AB_11127596
Rabbit monoclonal anti-cMET (for co-IP and immunoblots)	Cell Signaling Technology	Cat# 8198; RRID: AB_10858224
Mouse monoclonal anti-ERK1/2	Santa Cruz Biotechnology	Cat# sc-514302; RRID: AB_2571739
Mouse monoclonal anti-Gαq	Santa Cruz Biotechnology	Cat# sc-365906; RRID: AB_10842057
Rabbit polyclonal anti-JNK	Cell Signaling Technology	Cat# 9252; RRID: AB_2250373
Rabbit monoclonal anti-Ki-67	Cell Signaling Technology	Cat# 9027; RRID: AB_2636984
Mouse monoclonal anti-NF-L	Proteintech	Cat# 60189-1-Ig; RRID: AB_10860271
Normal rabbit IgG	Cell Signaling Technology	Cat# 2729; RRID: AB_1031062
Rabbit monoclonal anti-phospho-cMET (Tyr1234/1235)	Cell Signaling Technology	Cat# 3077; RRID: AB_2143884
Rabbit monoclonal anti-p38	Cell Signaling Technology	Cat# 8690; RRID: AB_10999090
Goat polyclonal anti-phospho-ERK (Tyr204)	Santa Cruz Biotechnology	Cat# sc-7976; RRID: AB_2297323
Rabbit monoclonal anti-phospho-JNK (Thr183/Tyr185)	Cell Signaling Technology	Cat# 4668; RRID: AB_823588
Rabbit monoclonal anti-phospho-p38 (Thr180/Tyr182)	Cell Signaling Technology	Cat# 4511; RRID: AB_2139682
Rabbit monoclonal anti-phospho-PKCα (Thr638)	Proteintech	Cat# 29123-1-AP; RRID: AB_2918239
Rabbit polyclonal anti-phospho-PKCδ (Tyr311) Antibody	Cell Signaling Technology	Cat# 2055; RRID: AB_330876
Rabbit monoclonal anti-PKCα	Proteintech	Cat# 21991-1-AP; RRID: AB_2878965
Rabbit monoclonal anti-PKCδ	Cell Signaling Technology	Cat# 9616; RRID: AB_10949973
Mouse monoclonal anti-SYP	Santa Cruz Biotechnology	Cat# sc-17750; RRID: AB_628311
Rabbit monoclonal anti-FLAG	Sigma-Aldrich	Cat# F1804; RRID: AB_262044
Rabbit polyclonal anti-VAChT	Synaptic Systems	Cat# 139 103; RRID: AB_887864
Mouse monoclonal anti-β-actin	Santa Cruz Biotechnology	Cat# sc-69879; RRID: AB_1119529
Rabbit monoclonal anti-β-arrestin 2	Proteintech	Cat# 10171-1-AP; RRID: AB_10644158
Mouse monoclonal anti-p504S	Agilent Technologies	Cat# M361601-2; RRID: AB_2305454
Mouse monoclonal anti-p63 (for IHC double staining)	Roche	Cat# 790-4509; RRID: AB_2335989
Mouse monoclonal anti-p63 (for IHC single staining)	Santa Cruz Biotechnology	Cat# sc-25268; RRID: AB_628092
Goat anti-mouse IgG-HRP	Santa Cruz Biotechnology	Cat# sc-2031; RRID: AB_631737
Goat anti-Rabbit IgG-HRP	Cell Signaling Technology	Cat# 7074; RRID: AB_2099233
Mouse anti-goat IgG-HRP	Santa Cruz Biotechnology	Cat# sc-2354; RRID: AB_ 628490
Goat anti-mouse IgG (H&L) Alexa Fluor 488	Thermo Fisher Scientific	Cat# A32723; RRID: AB_ 2633275
Goat anti-rabbit IgG (H&L) Alexa Fluor 555	Thermo Fisher Scientific	Cat# A32732; RRID: AB_2633281
Bacterial and virus strains
pLKO.1-puro non-mammalian shRNA control lentiviral particles	Sigma-Aldrich	Cat# SHC002V
pLKO.1-puro human CHRM1 shRNA#1 lentiviral particles	Sigma-Aldrich	Cat# SHCLNV_TRCN0000011250
pLKO.1-puro human CHRM1 shRNA#2 lentiviral particles	Sigma-Aldrich	Cat# SHCLNV_TRCN0000011251
Bacterial and virus strains Biological samples
Patient-derived xenograft (PDX)	University of Washington53	LuCaP 147CR
Subcloning efficiency DH5α competent cells	Thermo Fisher Scientific	Cat# 18-265-017
Chemicals, peptides, and recombinant proteins
Abiraterone acetate	MedChemExpress	Cat# HY-75054
Carbachol	VWR	Cat# AAL06674-03
Clozapine N-oxide	ApexBio	Cat# A3317
Crystal violet	Fisher Scientific	Cat# c581-25
Dicyclomine hydrochloride	Sigma-Aldrich	Cat# D7909
Docetaxel	Selleck Chemical	Cat# s1148
EGF recombinant human protein	Thermo Fisher Scientific	Cat# PHG0314
Enzalutamide	Selleck Chemical	Cat# S1250
Gefitinib	Selleck Chemical	Cat# S1025
bFGF recombinant human protein	Thermo Fisher Scientific	Cat# 13256-029
GM6001	Selleck Chemical	Cat# S7157
Human recombinant insulin solution	Sigma-Aldrich	Cat# I9278
McN-A-343	R & D systems	Cat# 1384/10
Mitoxantrone	MedChemExpress	Cat# HY-13502
M-MLV reverse transcriptase	Promega	Cat# PR-M1705
SB203580	MedChemExpress	Cat# HY-10256
SCH772984	MedChemExpress	Cat# HY-50846
Scopolamine hydrobromide	Sigma-Aldrich	Cat# S0929
SGX-523	MedChemExpress	Cat# HY-12019
SP600125	LC Laboratories	Cat# S-7979
Src inhibitor 1	Selleck Chemical	Cat# S6567
Tropicamide	MedChemExpress	Cat# HY-B0321
YM-254890	MedChemExpress	Cat# HY-111557
Halt protease and phosphatase inhibitor cocktail	Thermo Fisher Scientific	Cat# PI78443
Lipofectamine 2000 transfection reagent	Thermo Fisher Scientific	Cat# 11668027
Puromycin dihydrochloride	Thermo Fisher Scientific	Cat# A1113803
Low melt agarose	IBI Scientific	Cat# IB70051
B-27 supplement	Thermo Fisher Scientific	Cat# 17504044
Bovine serum albumin	Thermo Fisher Scientific	Cat# BP1600-100
Formaldehyde	Thermo Fisher Scientific	Cat# BP531500
Triton X-100	Thermo Fisher Scientific	Cat# BP151500
DAPI solution	Thermo Fisher Scientific	Cat# 62248
Tween 20	Thermo Fisher Scientific	Cat# BP337500
EcoRI	New England Biolabs	Cat# R0101S
XbaI	New England Biolabs	Cat# R0145T
Critical commercial assays
Pierce BCA Protein Assay Kit	Fisher Scientific	Cat# 23225
CellTiter-Glo Luminescent Cell Viability Assay	Promega	Cat# G7571
Duolink In Situ Red Starter Kit	Sigma-Aldrich	Cat# DUO92101
Fluo-8 Calcium Flux Assay Kit	Abcam	Cat# ab112129
Human HGF ELISA Kit	RayBiotech	Cat# ELH-HGF
In Situ Cell Death Detection Kit	Sigma-Aldrich	Cat# 12156792910
QIAquick Gel Extraction Kit	QIAGEN	Cat# 28706
Quickdetect Acetylcholine ELISA Kit	BioVision	Cat# E4452200524
QuickChange II XL Site-Directed Mutagenesis Kit	Agilent Technologies	Cat# E200524
QIAquick PCR Purification Kit	Qiagen	Cat# 28104
Quick Ligation Kit	VWR	Cat# M2200S
Pierce Co-Immunoprecipitation Kit	Thermo Fisher Scientific	Cat# 26149
RNeasy Mini Kit	Qiagen	Cat# 74104
Deposited data
RNA-seq raw data	This paper	GSE217749
Experimental models: Cell lines
22Rv1	ATCC	CRL-2505
DU145	ATCC	HTB-81
22Rv1DTXS	Dr. Milena Rizzo Lab (National Research Council of Italy, Pisa, Italy)12	N/A
22Rv1DTXR	Dr. Milena Rizzo Lab (National Research Council of Italy, Pisa, Italy)12	N/A
DU145DTXS	Dr. Zoran Culig Lab (Medical University of Innsbruck, Innsbruck, Austria)11	N/A
DU145DTXR	Dr. Zoran Culig Lab (Medical University of Innsbruck, Innsbruck, Austria)11	N/A
PC3DTXS	Dr. Zoran Culig Lab (Medical University of Innsbruck, Innsbruck, Austria)11	N/A
PC3DTXR	Dr. Zoran Culig Lab (Medical University of Innsbruck, Innsbruck, Austria)11	N/A
293T	ATCC	CRL-3216
COS-1	ATCC	CRL-1650
LNCaP	Dr. Leland Chung Lab (Cedars-Sinai Medical Center, Los Angeles, CA, USA)	N/A
PC3	ATCC	CRL-1435
LASCPC-01	ATCC	CRL-3356
NCI-H660	ATCC	CRL-5813
LAPC4	Dr. Michael Freeman Lab (Cedars-Sinai Medical Center, Los Angeles, CA, USA)	N/A
C4-2	Dr. Leland Chung Lab (Cedars-Sinai Medical Center, Los Angeles, CA, USA)	N/A
C4-2B	Dr. Leland Chung Lab (Cedars-Sinai Medical Center, Los Angeles, CA, USA)	N/A
C4-2BENZR	Dr. Allen Gao Lab (University of California, Davis, Davis, CA, USA)58	N/A
WPMY-1	ATCC	CRL-2854
PCF1	Dr. Leland Chung Lab (Cedars-Sinai Medical Center, Los Angeles, CA, USA)22	N/A
Experimental models: Organisms/strains
J:NU (nude) mice	Jackson Laboratory	Cat# 007850
NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice	Jackson Laboratory	Cat# 005557
Oligonucleotides
Human ChAT siRNA	Santa Cruz Biotech	Cat# sc-41919
Human β-arrestin-2 siRNA	Santa Cruz Biotech	Cat# sc-29208
Human CHRM1 siRNA	Origene	Cat# SR300807
Control siRNA	Santa Cruz Biotech	Cat# sc-37007
Recombinant DNA
pLVX-AcGFP1-N1	Takara Bio	Cat# 632154
pCMV-3×FLAG-Myc	Sigma-Aldrich	Cat# E6401
pLVX-CHRM1	This paper	N/A
pLVX-CHRM1-L167A	This paper	N/A
pLVX-CHRM1-C391A	This paper	N/A
pLVX-CHRM1-C394A	This paper	N/A
pLVX-CHRM1-P396A	This paper	N/A
pLVX-hM1Dq	Armbruster et al.25 and this paper	N/A
pLVX-FLAG-hM1Dq	This paper	N/A
pCMV-myc-ERK2-L4A-MEK1 fusion	Robinson et al.28	RRID: Addgene_39197
pcw107-FLAG-MKK7-JNK2 fusion	Martz et al.29	RRID: Addgene_64618
pcDNA3-FLAG-MKK6 (Glu)	Raingeaud et al.30	RRID: Addgene_13518
pCMV delta R8.2	Dr. Didier Trono Lab (Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland)	RRID: Addgene_12263
pCMV-VSV-G	Stewart et al.59	RRID: Addgene_8454
Software and algorithms
ImageJ	NIH	https://imagej.nih.gov/ij/
Image Lab 6.1	Bio-Rad Laboratories	https://www.bio-rad.com/en-us/product/image-lab-software
HALO	Indica Labs	https://indicalab.com/halo/
GSEA v4.0.3	Subramanian et al.60	https://www.gsea-msigdb.org/
GraphPad Prism 9	GraphPad	https://www.graphpad.com/
Bowtie 2 v2.1.0	SourceForge	https://bowtie-bio.sourceforge.net/
RSEM v1.2.15	Li and Dewey61	https://deweylab.github.io/RSEM/
AlphaFold Protein Structure Database	Varadi et al.62	https://alphafold.ebi.ac.uk/entry
Molecular Operating Environment (MOE) v2020.9	Chemical Computing Group ULC42	https://www.chemcomp.com/