Monounsaturated and Diunsaturated Fatty Acids Sensitize Cervical Cancer to Radiation Therapy.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
16 12 2022
16 12 2022
Historique:
received:
20
12
2021
revised:
27
07
2022
accepted:
05
10
2022
pubmed:
11
10
2022
medline:
20
12
2022
entrez:
10
10
2022
Statut:
ppublish
Résumé
Obesity induces numerous physiological changes that can impact cancer risk and patient response to therapy. Obese patients with cervical cancer have been reported to have superior outcomes following chemoradiotherapy, suggesting that free fatty acids (FFA) might enhance response to radiotherapy. Here, using preclinical models, we show that monounsaturated and diunsaturated FFAs (uFFA) radiosensitize cervical cancer through a novel p53-dependent mechanism. UFFAs signaled through PPARγ and p53 to promote lipid uptake, storage, and metabolism after radiotherapy. Stable isotope labeling confirmed that cervical cancer cells increase both catabolic and anabolic oleate metabolism in response to radiotherapy, with associated increases in dependence on mitochondrial fatty acid oxidation for survival. In vivo, supplementation with exogenous oleate suppressed tumor growth in xenografts after radiotherapy, an effect that could be partially mimicked in tumors from high fat diet-induced obese mice. These results suggest that supplementation with uFFAs may improve tumor responses to radiotherapy, particularly in p53 wild-type tumors. Metabolism of monounsaturated and diunsaturated fatty acids improves the efficacy of radiotherapy in cancer through modulation of p53 activity. See related commentary by Jungles and Green, p. 4513.
Identifiants
pubmed: 36214635
pii: 709678
doi: 10.1158/0008-5472.CAN-21-4369
pmc: PMC9772149
mid: NIHMS1852566
doi:
Substances chimiques
Fatty Acids
0
Oleic Acid
2UMI9U37CP
Tumor Suppressor Protein p53
0
Fatty Acids, Nonesterified
0
Fatty Acids, Monounsaturated
0
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
4515-4527Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK056341
Pays : United States
Organisme : NIEHS NIH HHS
ID : R35 ES028365
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2022 American Association for Cancer Research.
Références
Gastrointest Tumors. 2020 Apr;7(1-2):11-20
pubmed: 32399461
Cell Death Differ. 2016 Jul;23(7):1099-109
pubmed: 26967968
PLoS One. 2011 Feb 16;6(2):e16957
pubmed: 21359215
Protein Cell. 2021 Nov;12(11):836-857
pubmed: 33891303
Int J Cancer. 2003 Sep 20;106(5):752-7
pubmed: 12866036
Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):E4966-75
pubmed: 27506793
Cell. 2017 Oct 5;171(2):273-285
pubmed: 28985560
Cell Cycle. 2011 Jul 15;10(14):2344-54
pubmed: 21654191
Cancer Prev Res (Phila). 2011 Apr;4(4):486-501
pubmed: 21233290
Nature. 2019 Nov;575(7784):688-692
pubmed: 31634900
Cancer Res. 2018 Mar 15;78(6):1392-1403
pubmed: 29339540
Int J Radiat Oncol Biol Phys. 2020 Feb 1;106(2):369-376
pubmed: 31678226
ACS Chem Biol. 2020 Feb 21;15(2):469-484
pubmed: 31899616
Clin Oncol (R Coll Radiol). 2020 Sep;32(9):591-608
pubmed: 32595101
Nat Commun. 2019 Apr 8;10(1):1617
pubmed: 30962421
Nat Chem Biol. 2017 Jan;13(1):91-98
pubmed: 27842070
Urology. 2008 Aug;72(2):406-11
pubmed: 18267336
Mol Cancer Ther. 2020 Dec;19(12):2465-2475
pubmed: 33087507
Jpn J Clin Oncol. 2002 Jul;32(7):238-43
pubmed: 12324573
Cell. 2014 Jan 16;156(1-2):317-331
pubmed: 24439385
Oral Oncol. 2018 Aug;83:11-17
pubmed: 30098765
Cancers (Basel). 2020 Aug 19;12(9):
pubmed: 32825010
Oncogene. 2016 Oct 27;35(43):5663-5673
pubmed: 27065330
Breast Cancer Res Treat. 2018 Nov;172(1):221-230
pubmed: 30022328
Int J Gynecol Cancer. 2011 Aug;21(6):1117-23
pubmed: 21792015
Nature. 2019 May;569(7755):270-274
pubmed: 31043744
Clin Cancer Res. 2021 Aug 1;27(15):4245-4255
pubmed: 33820781
Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):561-566
pubmed: 29295932
Cancer. 2007 Dec 15;110(12):2691-9
pubmed: 17999404
BJU Int. 2010 Jan;105(1):42-8
pubmed: 19519759
Cancer Discov. 2019 Dec;9(12):1673-1685
pubmed: 31554642
Oncotarget. 2017 Dec 23;9(3):4061-4073
pubmed: 29423104
J Proteome Res. 2020 Apr 3;19(4):1447-1458
pubmed: 31984744
Semin Radiat Oncol. 2019 Jan;29(1):33-41
pubmed: 30573182
Mol Endocrinol. 2006 Dec;20(12):3083-92
pubmed: 16887883
N Engl J Med. 2003 Apr 24;348(17):1625-38
pubmed: 12711737
Diabetes. 2015 Feb;64(2):353-9
pubmed: 25157091
Cell Chem Biol. 2019 Mar 21;26(3):420-432.e9
pubmed: 30686757
Cancer. 2007 Oct 15;110(8):1738-44
pubmed: 17786947
Cancer. 2019 May 15;125(10):1588-1592
pubmed: 30633328