The FABP12/PPARγ pathway promotes metastatic transformation by inducing epithelial-to-mesenchymal transition and lipid-derived energy production in prostate cancer cells.
Cell Line, Tumor
Cell Movement
/ genetics
Cell Transformation, Neoplastic
/ pathology
Disease Progression
Energy Metabolism
Epithelial-Mesenchymal Transition
Fatty Acid-Binding Proteins
/ genetics
Gene Dosage
Humans
Lipids
/ chemistry
Male
Neoplasm Invasiveness
Neoplasm Metastasis
PPAR gamma
/ metabolism
Prostatic Neoplasms
/ metabolism
Signal Transduction
Xenograft Model Antitumor Assays
bioenergetics
epithelial-mesenchymal transition
fatty acid-binding proteins
metastasis
peroxisome proliferator-activated receptor gamma
prostate cancer
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
15
05
2020
revised:
11
08
2020
accepted:
05
10
2020
pubmed:
9
10
2020
medline:
4
9
2021
entrez:
8
10
2020
Statut:
ppublish
Résumé
Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid-binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial-to-mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid β-oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPARγ activation which, in turn, regulates FABP12's role in lipid metabolism and PCa progression. Our results point to a novel role for a FABP-PPAR pathway in promoting PCa metastasis through induction of EMT and lipid bioenergetics.
Identifiants
pubmed: 33031638
doi: 10.1002/1878-0261.12818
pmc: PMC7718947
doi:
Substances chimiques
FABP12 protein, human
0
Fatty Acid-Binding Proteins
0
Lipids
0
PPAR gamma
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3100-3120Informations de copyright
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Références
Oncogene. 2019 Sep;38(37):6445-6460
pubmed: 31324889
PPAR Res. 2012;2012:968040
pubmed: 23213321
Cancer Res. 2004 Jun 1;64(11):3814-22
pubmed: 15172988
Nat Protoc. 2007;2(2):329-33
pubmed: 17406593
Int J Cancer. 2014 Dec 1;135(11):2558-68
pubmed: 24740818
PPAR Res. 2010;2010:
pubmed: 20847935
Oncotarget. 2017 May 23;8(21):35376-35389
pubmed: 28430640
Int J Oncol. 2008 Apr;32(4):767-75
pubmed: 18360704
Clin Cancer Res. 2003 Jan;9(1):1-9
pubmed: 12538445
PPAR Res. 2017;2017:9456020
pubmed: 29181019
Genes Cancer. 2013 Jul;4(7-8):297-314
pubmed: 24167657
Mol Cancer. 2015 Jul 05;14:129
pubmed: 26142905
PLoS One. 2014 Jun 12;9(6):e99630
pubmed: 24925287
Genomics. 2008 Dec;92(6):436-45
pubmed: 18786628
Cell Signal. 2019 Oct;62:109336
pubmed: 31170472
J Cell Physiol. 2016 Dec;231(12):2664-72
pubmed: 26945682
Stem Cells Int. 2017;2017:1656053
pubmed: 28883835
Cancer. 2014 Mar 15;120(6):818-23
pubmed: 24258693
Nat Rev Endocrinol. 2015 Oct;11(10):592-605
pubmed: 26260145
Oncogene. 2003 May 8;22(18):2739-49
pubmed: 12743598
J Biomed Biotechnol. 2011;2011:567305
pubmed: 22007144
Crit Rev Oncol Hematol. 2018 Jan;121:11-22
pubmed: 29279096
Mol Biosyst. 2015 Dec;11(12):3397-406
pubmed: 26474270
Sci Transl Med. 2019 Feb 6;11(478):
pubmed: 30728288
Oncology. 2011;80(1-2):1-11
pubmed: 21577012
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Sci Rep. 2019 Dec 12;9(1):18944
pubmed: 31831821
J Exp Ther Oncol. 2004 Jul;4(2):91-100
pubmed: 15500004
Prostate Cancer Prostatic Dis. 2006;9(3):230-4
pubmed: 16683009
Lab Invest. 2002 May;82(5):629-37
pubmed: 12004003
Mol Oncol. 2014 Oct;8(7):1355-64
pubmed: 24910389
Nature. 2007 Jun 21;447(7147):959-65
pubmed: 17554340
Oncotarget. 2013 Nov;4(11):2108-23
pubmed: 24240026
Cancer Treat Rev. 2019 May;75:20-26
pubmed: 30875581
Cancer Cell. 2010 Jul 13;18(1):11-22
pubmed: 20579941
Cell Metab. 2014 Mar 4;19(3):393-406
pubmed: 24606897
Cell Death Dis. 2020 Feb 6;11(2):105
pubmed: 32029741
Dis Model Mech. 2018 May 3;11(8):
pubmed: 29739810
Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1364-70
pubmed: 17585059
Oncotarget. 2017 Dec 4;8(67):111780-111794
pubmed: 29340091
Int J Oncol. 2014 Jan;44(1):265-75
pubmed: 24189640
Genes Chromosomes Cancer. 2005 Dec;44(4):438-49
pubmed: 16130124
Cell Mol Life Sci. 2011 Sep;68(18):3033-46
pubmed: 21637948
BMC Cancer. 2011 Jul 18;11:302
pubmed: 21767383
Annu Rev Nutr. 2008;28:73-95
pubmed: 18435590
Nucl Med Biol. 2014 Mar;41(3):254-8
pubmed: 24440212
Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8290-5
pubmed: 27357679
Eur Urol. 2007 Jul;52(1):3-4
pubmed: 17467164
Oncogenesis. 2016 Jan 25;5:e189
pubmed: 26807644
Nutr J. 2014 Feb 14;13:17
pubmed: 24524207
Biomed Res Int. 2013;2013:824563
pubmed: 23762859
Nat Genet. 2018 Feb;50(2):206-218
pubmed: 29335545
Am J Clin Exp Urol. 2014 Jul 12;2(2):111-20
pubmed: 25374912
Front Oncol. 2017 Mar 14;7:40
pubmed: 28352611
Gene. 2018 Nov 15;676:171-183
pubmed: 30021130
Neoplasia. 2006 Dec;8(12):1083-9
pubmed: 17217626
Genes Cancer. 2019 May;10(3-4):80-96
pubmed: 31258834
Oncotarget. 2016 Dec 13;7(50):82783-82797
pubmed: 27779102
Exp Cell Res. 2010 Dec 10;316(20):3478-88
pubmed: 20932825
Mol Aspects Med. 2004 Oct-Dec;25(5-6):495-520
pubmed: 15363638
Biotechniques. 2009 Apr;46(4):265-74
pubmed: 19450233
J Pathol. 2012 Nov;228(3):310-21
pubmed: 22322885
Bioinformatics. 2013 Oct 15;29(20):2588-95
pubmed: 23975762
Prostate. 2012 Feb 1;72(2):129-46
pubmed: 21538422
Prog Lipid Res. 2004 Jul;43(4):328-49
pubmed: 15234551
Mol Cancer Ther. 2014 Oct;13(10):2361-71
pubmed: 25122071
Cancer Res. 2007 Sep 1;67(17):8229-39
pubmed: 17804737
Trends Cell Biol. 2014 Aug;24(8):472-8
pubmed: 24985940
Oncotarget. 2016 Feb 23;7(8):9322-39
pubmed: 26814431
Int J Oncol. 2010 Jan;36(1):69-76
pubmed: 19956834
Int J Mol Sci. 2019 May 28;20(11):
pubmed: 31142021
Cell Metab. 2017 Feb 7;25(2):228-230
pubmed: 28178563
Cancer Metastasis Rev. 2011 Dec;30(3-4):325-42
pubmed: 22048864
Asian J Androl. 2018 May-Jun;20(3):238-243
pubmed: 28597850
Math Med Biol. 2012 Mar;29(1):49-65
pubmed: 20610469
Lipids. 2008 Jan;43(1):1-17
pubmed: 17882463
J Appl Genet. 2006;47(1):39-48
pubmed: 16424607
Clin Cancer Res. 2001 Jun;7(6):1706-15
pubmed: 11410510
Cancer Res. 2004 Mar 1;64(5):1589-94
pubmed: 14996714
Eur Urol. 2007 Aug;52(2):331-43
pubmed: 17507151
J Neurochem. 2017 Jan;140(1):96-113
pubmed: 27787894
Mol Cancer Res. 2019 May;17(5):1166-1179
pubmed: 30808729
Mol Cancer. 2017 Apr 11;16(1):76
pubmed: 28399876
J Cell Sci. 2003 Feb 1;116(Pt 3):499-511
pubmed: 12508111