The oncogene AAMDC links PI3K-AKT-mTOR signaling with metabolic reprograming in estrogen receptor-positive breast cancer.

Antineoplastic Agents / pharmacology Breast Neoplasms / genetics Cell Cycle Proteins / genetics Everolimus / pharmacology Female GTPase-Activating Proteins / metabolism Gene Expression Regulation, Neoplastic Humans Imidazoles / pharmacology Nerve Tissue Proteins / metabolism Oncogenes / genetics Phosphatidylinositol 3-Kinases / metabolism Protein Binding Proto-Oncogene Proteins c-akt / metabolism Quinolines / pharmacology Receptors, Estrogen / metabolism Signal Transduction / drug effects TOR Serine-Threonine Kinases / metabolism

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
26 03 2021
Historique:
received: 31 10 2020
accepted: 25 02 2021
entrez: 27 3 2021
pubmed: 28 3 2021
medline: 13 4 2021
Statut: epublish

Résumé

Adipogenesis associated Mth938 domain containing (AAMDC) represents an uncharacterized oncogene amplified in aggressive estrogen receptor-positive breast cancers. We uncover that AAMDC regulates the expression of several metabolic enzymes involved in the one-carbon folate and methionine cycles, and lipid metabolism. We show that AAMDC controls PI3K-AKT-mTOR signaling, regulating the translation of ATF4 and MYC and modulating the transcriptional activity of AAMDC-dependent promoters. High AAMDC expression is associated with sensitization to dactolisib and everolimus, and these PI3K-mTOR inhibitors exhibit synergistic interactions with anti-estrogens in IntClust2 models. Ectopic AAMDC expression is sufficient to activate AKT signaling, resulting in estrogen-independent tumor growth. Thus, AAMDC-overexpressing tumors may be sensitive to PI3K-mTORC1 blockers in combination with anti-estrogens. Lastly, we provide evidence that AAMDC can interact with the RabGTPase-activating protein RabGAP1L, and that AAMDC, RabGAP1L, and Rab7a colocalize in endolysosomes. The discovery of the RabGAP1L-AAMDC assembly platform provides insights for the design of selective blockers to target malignancies having the AAMDC amplification.

Identifiants

DOI: 10.1038/s41467-021-22101-7 PMID: 33772001 PMC: PMC7998036
pubmed: 33772001
doi: 10.1038/s41467-021-22101-7
pii: 10.1038/s41467-021-22101-7
pmc: PMC7998036
doi:

Substances chimiques

AAMDC protein, human 0
Antineoplastic Agents 0
Cell Cycle Proteins 0
GTPase-Activating Proteins 0
Imidazoles 0
Nerve Tissue Proteins 0
Quinolines 0
RABGAP1L protein, human 0
Receptors, Estrogen 0
Everolimus 9HW64Q8G6G
MTOR protein, human EC 2.7.1.1
Proto-Oncogene Proteins c-akt EC 2.7.11.1
TOR Serine-Threonine Kinases EC 2.7.11.1
dactolisib RUJ6Z9Y0DT

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1920

Subventions

Organisme : NCI NIH HHS
ID : R01 CA170370
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA036906
Pays : United States
Organisme : NIH HHS
ID : S10 OD020025
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES027595
Pays : United States

Références

Nature. 2000 Aug 17;406(6797):747-52
pubmed: 10963602
Curr Biol. 2014 Oct 6;24(19):2274-80
pubmed: 25220053
Bioinformatics. 2009 May 1;25(9):1105-11
pubmed: 19289445
Cell. 2010 Apr 16;141(2):290-303
pubmed: 20381137
Mol Endocrinol. 2016 Aug;30(8):889-904
pubmed: 27355191
Science. 2005 Feb 18;307(5712):1098-101
pubmed: 15718470
Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):E11170-E11179
pubmed: 29229865
Br J Cancer. 2013 Feb 19;108(3):557-63
pubmed: 23361053
Oncotarget. 2015 Nov 10;6(35):37367-84
pubmed: 26452259
Mol Cancer Res. 2013 Oct;11(10):1269-78
pubmed: 23814023
Sci Rep. 2020 May 14;10(1):7950
pubmed: 32409632
Cell. 2015 Oct 22;163(3):712-23
pubmed: 26496610
Curr Med Chem. 2007;14(28):3035-45
pubmed: 18220739
J Biol Chem. 2006 Jun 16;281(24):16768-76
pubmed: 16608839
Proteins. 2001 Dec 1;45(4):486-8
pubmed: 11746696
Nat Protoc. 2015 Jun;10(6):845-58
pubmed: 25950237
Oncogene. 2014 Mar 27;33(13):1621-8
pubmed: 23686313
Elife. 2016 Oct 08;5:
pubmed: 27718357
Mol Genet Metab. 2017 Mar;120(3):235-242
pubmed: 28122681
Future Med Chem. 2015 Aug;7(12):1511-9
pubmed: 26306654
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
J Clin Oncol. 2016 Feb 10;34(5):419-26
pubmed: 26503204
Cancers (Basel). 2020 Jan 21;12(2):
pubmed: 31973201
Genome Biol. 2014;15(12):550
pubmed: 25516281
Endocr Relat Cancer. 2005 Sep;12(3):599-614
pubmed: 16172194
Oncotarget. 2016 Jan 5;7(1):176-92
pubmed: 26484415
Nat Commun. 2018 Apr 16;9(1):1475
pubmed: 29662076
Oncogene. 2019 Jan;38(1):140-150
pubmed: 30076412
Nat Methods. 2006 Mar;3(3):165-74
pubmed: 16489332
N Engl J Med. 2018 Jul 12;379(2):111-121
pubmed: 29860917
J Clin Invest. 2010 Jul;120(7):2406-13
pubmed: 20530877
FEBS Lett. 2019 Jul;593(14):1724-1734
pubmed: 31116411
Free Radic Biol Med. 2015 Sep;86:228-38
pubmed: 26051168
Breast Cancer Res Treat. 2010 Oct;123(3):725-31
pubmed: 20020197
Adv Enzyme Regul. 1984;22:27-55
pubmed: 6382953
Cell Rep. 2017 May 9;19(6):1083-1090
pubmed: 28494858
Mol Ther Nucleic Acids. 2019 Mar 1;14:287-300
pubmed: 30654190
Adv Ther. 2013 Oct;30(10):870-84
pubmed: 24158787
Science. 2015 Oct 9;350(6257):211-7
pubmed: 26338797
Mol Cell. 2010 Jul 30;39(2):171-83
pubmed: 20670887
J Clin Oncol. 2009 Mar 10;27(8):1160-7
pubmed: 19204204
F1000Res. 2015 Dec 30;4:1521
pubmed: 26925227
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Cell. 2014 Feb 13;156(4):771-85
pubmed: 24529379
Curr Biol. 1997 Apr 1;7(4):261-9
pubmed: 9094314
Cancer Cell. 2014 Nov 10;26(5):754-69
pubmed: 25446900
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74
pubmed: 11553815
Cancer Chemother Pharmacol. 2018 Aug;82(2):285-298
pubmed: 29882016
Cancer Res. 2009 Oct 1;69(19):7491-4
pubmed: 19773439
Cell Metab. 2013 Oct 1;18(4):465-9
pubmed: 23973332
Hum Mol Genet. 2017 Dec 1;26(23):4541-4555
pubmed: 28973657
Cancer Res. 2014 Apr 15;74(8):2258-69
pubmed: 24566868
Sci Transl Med. 2015 Apr 15;7(283):283ra51
pubmed: 25877889
Blood. 2008 Sep 15;112(6):2305-17
pubmed: 18621930
Nat Protoc. 2006;1(1):337-45
pubmed: 17406254
EMBO Rep. 2013 May;14(5):450-7
pubmed: 23478338
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
J Cell Physiol. 2012 Jun;227(6):2788-97
pubmed: 21928319
Science. 2016 Feb 12;351(6274):728-733
pubmed: 26912861
Carcinogenesis. 2012 Mar;33(3):509-18
pubmed: 22180571
J Cell Biol. 2017 Jul 3;216(7):2027-2045
pubmed: 28566324
J Biol Chem. 2017 Mar 17;292(11):4411-4422
pubmed: 28130450
J Biol Chem. 1997 Jan 24;272(4):2163-6
pubmed: 8999918
J Nutr. 2012 Mar;142(3):448-55
pubmed: 22279136
Nature. 2012 Apr 18;486(7403):346-52
pubmed: 22522925
Oncogene. 1998 Aug 13;17(6):769-80
pubmed: 9715279

Auteurs

Emily Golden (E)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.
Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.

Rabab Rashwan (R)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.
Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.
Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt.

Eleanor A Woodward (EA)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.
Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.

Agustin Sgro (A)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.
Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.
School of Human Sciences, The University of Western Australia, Perth, WA, Australia.

Edina Wang (E)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.
Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.

Anabel Sorolla (A)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.
Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.
ORCID: 0000-0001-8238-8763

Charlene Waryah (C)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.
Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.

Wan Jun Tie (WJ)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.
Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.

Elisabet Cuyàs (E)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.
Girona Biomedical Research Institute, Girona, Catalonia, Spain.
ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain.

Magdalena Ratajska (M)

Department of Biology and Medical Genetics, Medical University of Gdansk, Gdansk, Poland.
The Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia.
Department of Pathology, Otago University, Dunedin, New Zealand.
ORCID: 0000-0001-7015-1865

Iwona Kardaś (I)

Department of Biology and Medical Genetics, Medical University of Gdansk, Gdansk, Poland.
Laboratory of Clinical Genetics, University Clinical Centre, Gdansk, Poland.

Piotr Kozlowski (P)

Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
ORCID: 0000-0003-3770-7715

Elizabeth K M Johnstone (EKM)

Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.
Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
Australian Research Council Centre for Personalised Therapeutics Technologies, Melbourne and Perth, Australia.
ORCID: 0000-0001-7990-371X

Heng B See (HB)

Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.
Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
Australian Research Council Centre for Personalised Therapeutics Technologies, Melbourne and Perth, Australia.

Ciara Duffy (C)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.
Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.
School of Human Sciences, The University of Western Australia, Perth, WA, Australia.

Jeremy Parry (J)

Department of Anatomical Pathology, Path West Laboratory, Fiona Stanley Hospital Network, Murdoch, WA, Australia.

Kim A Lagerborg (KA)

Departments of Medicine and Pharmacology, University of California, San Diego, CA, USA.
ORCID: 0000-0002-9101-0022

Piotr Czapiewski (P)

Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland.
Institute of Pathology, Dessau Medical Centre, Dessau, Germany.

Javier A Menendez (JA)

Girona Biomedical Research Institute, Girona, Catalonia, Spain.
ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain.

Adam Gorczyński (A)

Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland.

Bartosz Wasag (B)

Department of Biology and Medical Genetics, Medical University of Gdansk, Gdansk, Poland.
Laboratory of Clinical Genetics, University Clinical Centre, Gdansk, Poland.
ORCID: 0000-0002-3634-7562

Kevin D G Pfleger (KDG)

Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.
Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
Australian Research Council Centre for Personalised Therapeutics Technologies, Melbourne and Perth, Australia.
Dimerix Limited, Nedlands, WA, Australia.

Christina Curtis (C)

Stanford University School of Medicine (Departments of Medicine & Genetics) and Stanford Cancer Institute, Stanford, CA, USA.
ORCID: 0000-0003-0166-3802

Bum-Kyu Lee (BK)

Department of Biomedical Sciences, Cancer Research Center, University at Albany-State University of New York, Rensselaer, NY, USA.

Jonghwan Kim (J)

Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA.
ORCID: 0000-0002-9919-9843

Joseph Cursons (J)

Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
ORCID: 0000-0002-5053-4540

Nathan J Pavlos (NJ)

The Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia.
School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia.

Wojciech Biernat (W)

Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland.
ORCID: 0000-0001-8462-2189

Mohit Jain (M)

Departments of Medicine and Pharmacology, University of California, San Diego, CA, USA.

Andrew J Woo (AJ)

Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.
School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia.
ORCID: 0000-0003-1198-6373

Andrew Redfern (A)

School of Medicine, University of Western Australia, Perth, WA, Australia.

Pilar Blancafort (P)

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia. pilar.blancafort@uwa.edu.au.
Centre for Medical Research, The University of Western Australia, Perth, WA, Australia. pilar.blancafort@uwa.edu.au.
School of Human Sciences, The University of Western Australia, Perth, WA, Australia. pilar.blancafort@uwa.edu.au.
The Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. pilar.blancafort@uwa.edu.au.
ORCID: 0000-0002-3881-7396

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines du cycle cellulaire › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Composés chimiques organiques › Lactones › Sirolimus › Évérolimus › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Régulateurs des protéines G › Protéines d'activation de la GTPase › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Imidazoles › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes tumoraux › Oncogènes › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphatidylinositol 3-kinases › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Métabolisme › Liaison aux protéines › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes c-akt › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinoléines › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs aux stéroïdes › Récepteurs des oestrogènes › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Phénomènes physiologiques cellulaires › Transduction du signal › The oncogene AAMDC links PI3K-AKT-mTOR...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › The oncogene AAMDC links PI3K-AKT-mTOR...