MBTPS1 regulates proliferation of colorectal cancer primarily through its action on sterol regulatory element-binding proteins.
CRISPR/Cas9
HT-29
MBTPS1
SKI-1/S1P
SREBP
colon cancer
lipid metabolism
site-1 protease
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2022
2022
Historique:
received:
26
07
2022
accepted:
05
09
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
28
10
2022
Statut:
epublish
Résumé
Among the main metabolic pathways implicated in cancer cell proliferation are those of cholesterol and fatty acid synthesis, both of which are tightly regulated by sterol regulatory element-binding proteins (SREBPs). SREBPs are activated through specific cleavage by membrane-bound transcription factor protease 1 (MBTPS1), a serine protease that cleaves additional substrates (ATF6, BDNF, CREBs and somatostatin), some of which are also implicated in cell proliferation. The goal of this study was to determine whether MBTPS1 may serve as a master regulator in proliferation of colorectal cancer (CRC). Tumors from CRC patients showed variable levels of MBTPS1 mRNA, which were in positive correlation with the levels of SREBPs and ATF6, and in reverse correlation with BDNF levels. Chemical inhibition of MBTPS1 activity in two CRC-derived cell lines resulted in a marked decrease in the levels of SREBPs, but not of its other substrates and a marked decrease in cell proliferation, which suggested that MBTPS1 activity is critical for proliferation of these cells. In accordance, CRISPR/Cas9 targeted knockout (KO) of the
Identifiants
pubmed: 36300096
doi: 10.3389/fonc.2022.1004014
pmc: PMC9592115
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1004014Informations de copyright
Copyright © 2022 Hartal-Benishay, Saadi, Toubiana, Shaked, Lalzar, Abu Hatoum, Tal, Selig and Barki-Harrington.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Br J Cancer. 1997;75(10):1509-14
pubmed: 9166946
Science. 2011 Jul 1;333(6038):87-90
pubmed: 21719679
Mol Oncol. 2018 Oct;12(10):1706-1717
pubmed: 30063110
J Cell Sci. 2016 Sep 15;129(18):3367-73
pubmed: 27635066
Mol Biol Cell. 2006 Jan;17(1):413-26
pubmed: 16236796
Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1321-6
pubmed: 9990022
Regul Pept. 2004 Aug 15;120(1-3):133-40
pubmed: 15177931
Exp Ther Med. 2013 Dec;6(6):1475-1481
pubmed: 24255678
Mol Cell Biol. 2002 Aug;22(16):5639-49
pubmed: 12138176
Biochem J. 1999 Mar 15;338 ( Pt 3):569-82
pubmed: 10051425
Cell Metab. 2017 Feb 7;25(2):262-284
pubmed: 28178565
Nat Protoc. 2013 Nov;8(11):2281-2308
pubmed: 24157548
J Invest Dermatol. 2014 Jan;134(1):168-175
pubmed: 23884247
Endocr Relat Cancer. 2015 Jun;22(3):455-64
pubmed: 25876647
Nat Rev Cancer. 2016 Nov;16(11):718-731
pubmed: 27562463
Int J Mol Sci. 2020 Apr 30;21(9):
pubmed: 32366045
Mol Cell Endocrinol. 1994 Mar;99(2):307-14
pubmed: 8206338
Nature. 2021 Mar;591(7849):306-311
pubmed: 33627871
Mol Cell. 2000 Dec;6(6):1355-64
pubmed: 11163209
Biochem Pharmacol. 2020 Apr;174:113776
pubmed: 31874145
Cell Death Dis. 2018 Feb 15;9(3):265
pubmed: 29449559
Diabetes. 2016 Jul;65(7):1904-15
pubmed: 27207533
Cell. 2000 Feb 18;100(4):391-8
pubmed: 10693756
Mol Cell. 1998 Oct;2(4):505-14
pubmed: 9809072
Biotechnol Bioeng. 2011 Dec;108(12):2777-93
pubmed: 21809331
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12027-32
pubmed: 14512514
Innate Immun. 2012 Apr;18(2):294-306
pubmed: 21733977
Mol Cell Biol. 2000 Mar;20(5):1868-76
pubmed: 10669761
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11041-8
pubmed: 10500120
Biochem J. 2004 Jul 15;381(Pt 2):357-63
pubmed: 15084148
Dev Cell. 2018 Aug 6;46(3):327-343.e7
pubmed: 30086303
Curr Protoc. 2021 Mar;1(3):e90
pubmed: 33780170
Adv Drug Deliv Rev. 2008 Apr 29;60(7):805-12
pubmed: 18262679
Cell Metab. 2020 Jan 7;31(1):62-76
pubmed: 31813823
J Biol Chem. 2001 Aug 17;276(33):30686-93
pubmed: 11402025
Front Microbiol. 2021 Jan 28;12:583834
pubmed: 33584607
Gastroenterology. 2018 Nov;155(5):1539-1552.e12
pubmed: 30063920
Cell Signal. 2013 Aug;25(8):1678-88
pubmed: 23665374
Nat Rev Endocrinol. 2017 Dec;13(12):710-730
pubmed: 28849786
Mol Carcinog. 2005 Nov;44(3):151-61
pubmed: 16167351
J Biol Chem. 2000 Jan 28;275(4):2349-58
pubmed: 10644685
Bioorg Med Chem Lett. 2007 Aug 15;17(16):4411-4
pubmed: 17583500
Biochim Biophys Acta. 2007 Jun;1768(6):1311-24
pubmed: 17493580
Exp Cell Res. 2000 Nov 25;261(1):159-65
pubmed: 11082286
Front Cell Dev Biol. 2019 Jul 03;7:123
pubmed: 31334233
Virology. 2012 Feb 5;423(1):14-22
pubmed: 22154237
Biochem Biophys Res Commun. 2017 Aug 26;490(3):760-766
pubmed: 28645614