Stromal-derived MAOB promotes prostate cancer growth and progression.
Prostate cancer (PC) develops in a microenvironment where the stromal cells modulate adjacent tumor growth and progression. Here, we demonstrated elevated levels of monoamine oxidase B (MAOB), a mitochondrial enzyme that degrades biogenic and dietary monoamines, in human PC stroma, which was associated with poor clinical outcomes of PC patients. Knockdown or overexpression of MAOB in human prostate stromal fibroblasts indicated that MAOB promotes cocultured PC cell proliferation, migration, and invasion and co-inoculated prostate tumor growth in mice. Mechanistically, MAOB induces a reactive stroma with activated marker expression, increased extracellular matrix remodeling, and acquisition of a protumorigenic phenotype through enhanced production of reactive oxygen species. Moreover, MAOB transcriptionally activates CXCL12 through Twist1 synergizing with TGFβ1-dependent Smads in prostate stroma, which stimulates tumor-expressed CXCR4-Src/JNK signaling in a paracrine manner. Pharmacological inhibition of stromal MAOB restricted PC xenograft growth in mice. Collectively, these findings characterize the contribution of MAOB to PC and suggest MAOB as a potential stroma-based therapeutic target.
Pubmed ID: 38335292 RIS Download
Research resources used in this publication
Additional research tools detected in this publication
- Addgene (RRID:SCR_002037)
- Gene Set Enrichment Analysis (RRID:SCR_003199)
- Sino Biological (RRID:SCR_003697)
- Novus Biologicals (RRID:SCR_004286)
- Bowtie (RRID:SCR_005476)
- RayBiotech (RRID:SCR_005517)
- Bioconductor (RRID:SCR_006442)
- Promega (RRID:SCR_006724)
- PeproTech (RRID:SCR_006802)
- Thermo Fisher Scientific (RRID:SCR_008452)
- Proteintech Group (RRID:SCR_008986)
- Santa Cruz Biotechnology (RRID:SCR_008987)
- Sigma-Aldrich (RRID:SCR_008988)
- Abcam (RRID:SCR_012931)
- BD Biosciences (RRID:SCR_013311)
- Agilent Technologies (RRID:SCR_013575)
- Living Image software (RRID:SCR_014247)
Antibodies used in this publication
- Stromal Derived Factor-1, CXCL12 (RRID:AB_2088149)
- Androgen Receptor (D6F11) XP Rabbit mAb (RRID:AB_10691711)
- Ki-67 (D2H10) Rabbit mAb (IHC Specific) (RRID:AB_2636984)
- SYP (D-4) (RRID:AB_628311)
- Chr-A Antibody (C-12) (RRID:AB_2801371)
- Normal Rabbit IgG (RRID:AB_1031062)
- SMAD4 (D3R4N) XP (RRID:AB_2736998)
- Human/Mouse CXCL12/SDF-1 MAb (Clone 79014) (RRID:AB_2276927)
- lactoferrin (1B8) (RRID:AB_1123605)
- FoxO1 (C29H4) Rabbit mAb (RRID:AB_2106495)
- Phospho-FoxO1 (Ser256) Antibody (RRID:AB_329831)
- Akt (pan) (C67E7) Rabbit mAb (RRID:AB_915783)
- Phospho-Akt (Ser473) (D9E) XP® Rabbit mAb (RRID:AB_2315049)
- Mouse Anti-Human HIF-1α Clone 54/HIF-1α (RRID:AB_398272)
- CREB (48H2) Rabbit mAb (RRID:AB_331277)
- p-CREB-1 (10E9) (RRID:AB_1125727)
- BAD antibody (RRID:AB_2061994)
- Rabbit Anti-Bad, phospho (Ser112) Monoclonal Antibody, Unconjugated, Clone 40A9 (RRID:AB_560884)
- JAK1 antibody (RRID:AB_2881834)
- JAK1 Antibody (RRID:AB_1144529)
- c-Kit/CD117 antibody (RRID:AB_2249558)
- Anti-c-Kit (pTyr721) Antibody (RRID:AB_895204)
- Caspase 9/p35/p10 antibody (RRID:AB_2068632)
- Phospho-Caspase 9 (Ser196) antibody (RRID:AB_2881214)
- SAPK/JNK Antibody (RRID:AB_2250373)
- Phospho-SAPK/JNK (Thr183/Tyr185) (81E11) Rabbit mAb (RRID:AB_823588)
- c-Src (B-12) (RRID:AB_627306)
- CXCR7 antibody [C1C2], Internal (RRID:AB_1240639)
- Twist-1 Antibody (10E4E6) (RRID:AB_2801339)
- Smad3 (C67H9) Rabbit mAb (RRID:AB_2193182)
- Phospho-Smad3 (Ser423/425) (C25A9) Rabbit mAb (RRID:AB_2193207)
- Smad2 (D43B4) XP Rabbit mAb (RRID:AB_10626777)
- Phospho-Smad2 (Ser465/467) (138D4) Rabbit mAb (RRID:AB_490941)
- Anti-MAOB polyclonal antibody (RRID:AB_1854062)
Associated grants
- Agency: NCI NIH HHS, United States
Id: P01 CA163227 - Agency: NCI NIH HHS, United States
Id: P50 CA097186 - Agency: NCI NIH HHS, United States
Id: R01 CA258634 - Agency: NCI NIH HHS, United States
Id: R37 CA233658
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This is a list of tools and resources that we have found mentioned in this publication.
Addgene (tool)
RRID:SCR_002037
Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsGene Set Enrichment Analysis (tool)
RRID:SCR_003199
Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsNovus Biologicals (tool)
RRID:SCR_004286
Commercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsBowtie (tool)
RRID:SCR_005476
Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.
View all literature mentionsBioconductor (tool)
RRID:SCR_006442
Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.
View all literature mentionsThermo Fisher Scientific (tool)
RRID:SCR_008452
Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsProteintech Group (tool)
RRID:SCR_008986
Proteintech Europe Ltd is an ISO 9001:2008 certified company
View all literature mentionsSigma-Aldrich (tool)
RRID:SCR_008988
American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsAbcam (tool)
RRID:SCR_012931
A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsAgilent Technologies (tool)
RRID:SCR_013575
Company provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.
View all literature mentionsLiving Image software (tool)
RRID:SCR_014247
In vivo imaging software which facilitates workflow for in vivo optical, X-ray and microCT image acquisition, analysis and data organization.
View all literature mentionsStromal Derived Factor-1, CXCL12 (antibody)
RRID:AB_2088149
This monoclonal targets Recombinant Human SDF1
View all literature mentionsAndrogen Receptor (D6F11) XP Rabbit mAb (antibody)
RRID:AB_10691711
This monoclonal targets Androgen Receptor (D6F11) XP Rabbit mAb
View all literature mentionsKi-67 (D2H10) Rabbit mAb (IHC Specific) (antibody)
RRID:AB_2636984
This monoclonal targets Ki-67
View all literature mentionsChr-A Antibody (C-12) (antibody)
RRID:AB_2801371
This monoclonal targets Chr-A
View all literature mentionsNormal Rabbit IgG (antibody)
RRID:AB_1031062
This isotype control targets not applicable
View all literature mentionsSMAD4 (D3R4N) XP (antibody)
RRID:AB_2736998
This monoclonal targets Smad4
View all literature mentionsHuman/Mouse CXCL12/SDF-1 MAb (Clone 79014) (antibody)
RRID:AB_2276927
This monoclonal targets Human/Mouse CXCL12/SDF-1 MAb (Clone 79014)
View all literature mentionslactoferrin (1B8) (antibody)
RRID:AB_1123605
This monoclonal targets Human LTF
View all literature mentionsFoxO1 (C29H4) Rabbit mAb (antibody)
RRID:AB_2106495
This monoclonal targets FoxO1 (C29H4) Rabbit mAb
View all literature mentionsPhospho-FoxO1 (Ser256) Antibody (antibody)
RRID:AB_329831
This polyclonal targets Phospho-FoxO1 (Ser256)
View all literature mentionsAkt (pan) (C67E7) Rabbit mAb (antibody)
RRID:AB_915783
This monoclonal targets Akt (pan) (C67E7) Rabbit mAb
View all literature mentionsPhospho-Akt (Ser473) (D9E) XP® Rabbit mAb (antibody)
RRID:AB_2315049
This monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsMouse Anti-Human HIF-1α Clone 54/HIF-1α (antibody)
RRID:AB_398272
This monoclonal targets HIF-1a
View all literature mentionsCREB (48H2) Rabbit mAb (antibody)
RRID:AB_331277
This monoclonal targets CREB
View all literature mentionsp-CREB-1 (10E9) (antibody)
RRID:AB_1125727
This monoclonal targets p-CREB-1 (10E9)
View all literature mentionsRabbit Anti-Bad, phospho (Ser112) Monoclonal Antibody, Unconjugated, Clone 40A9 (antibody)
RRID:AB_560884
This monoclonal targets Bad, phospho (Ser112)
View all literature mentionsc-Kit/CD117 antibody (antibody)
RRID:AB_2249558
This polyclonal targets c-Kit/CD117
View all literature mentionsAnti-c-Kit (pTyr721) Antibody (antibody)
RRID:AB_895204
This polyclonal targets c-Kit (pTyr721)
View all literature mentionsCaspase 9/p35/p10 antibody (antibody)
RRID:AB_2068632
This polyclonal targets Caspase 9/p35/p10
View all literature mentionsPhospho-Caspase 9 (Ser196) antibody (antibody)
RRID:AB_2881214
This polyclonal targets Phospho-Caspase 9 (Ser196)
View all literature mentionsSAPK/JNK Antibody (antibody)
RRID:AB_2250373
This polyclonal targets SAPK/JNK
View all literature mentionsPhospho-SAPK/JNK (Thr183/Tyr185) (81E11) Rabbit mAb (antibody)
RRID:AB_823588
This polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)
View all literature mentionsc-Src (B-12) (antibody)
RRID:AB_627306
This monoclonal targets c-Src (B-12)
View all literature mentionsCXCR7 antibody [C1C2], Internal (antibody)
RRID:AB_1240639
This polyclonal targets CXCR7
View all literature mentionsTwist-1 Antibody (10E4E6) (antibody)
RRID:AB_2801339
This monoclonal targets TWIST1
View all literature mentionsSmad3 (C67H9) Rabbit mAb (antibody)
RRID:AB_2193182
This monoclonal targets Smad3
View all literature mentionsPhospho-Smad3 (Ser423/425) (C25A9) Rabbit mAb (antibody)
RRID:AB_2193207
This monoclonal targets Phospho-Smad3 (Ser423/425) (C25A9) Rabbit mAb
View all literature mentionsSmad2 (D43B4) XP Rabbit mAb (antibody)
RRID:AB_10626777
This monoclonal targets Smad2 (D43B4) XP Rabbit mAb
View all literature mentionsPhospho-Smad2 (Ser465/467) (138D4) Rabbit mAb (antibody)
RRID:AB_490941
This monoclonal targets Phospho-Smad2 (Ser465/467) (138D4) Rabbit mAb
View all literature mentionsAnti-MAOB polyclonal antibody (antibody)
RRID:AB_1854062
This polyclonal targets MAOB
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsC.B-Igh-1/IcrTac-Prkdcscid (organism)
RRID:IMSR_TAC:CB17SC
Mus musculus with name C.B-Igh-1/IcrTac-Prkdcscid from IMSR.
View all literature mentions
NOD.Cg-Prkdcscid Il2rg/SzJ (organism)
RRID:IMSR_JAX:005557
Mus musculus with name NOD.Cg-Prkdcscid Il2rg
