Expression of oncogenic HRAS in human Rh28 and RMS-YM rhabdomyosarcoma cells leads to oncogene-induced senescence.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 08 2021
13 08 2021
Historique:
received:
03
04
2020
accepted:
06
07
2021
entrez:
14
8
2021
pubmed:
15
8
2021
medline:
12
11
2021
Statut:
epublish
Résumé
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. The two predominant histologic variants of RMS, embryonal and alveolar rhabdomyosarcoma (eRMS and aRMS, respectively), carry very different prognoses. While eRMS is associated with an intermediate prognosis, the 5-year survival rate of aRMS is less than 30%. The RMS subtypes are also different at the molecular level-eRMS frequently has multiple genetic alterations, including mutations in RAS and TP53, whereas aRMS often has chromosomal translocations resulting in PAX3-FOXO1 or PAX7-FOXO1 fusions, but otherwise has a "quiet" genome. Interestingly, mutations in RAS are rarely found in aRMS. In this study, we explored the role of oncogenic RAS in aRMS. We found that while ectopic oncogenic HRAS expression was tolerated in the human RAS-driven eRMS cell line RD, it was detrimental to cell growth and proliferation in the human aRMS cell line Rh28. Growth inhibition was mediated by oncogene-induced senescence and associated with increased RB pathway activity and expression of the cyclin-dependent kinase inhibitors p16 and p21. Unexpectedly, the human eRMS cell line RMS-YM, a RAS wild-type eRMS cell line, also exhibited growth inhibition in response to oncogenic HRAS in a manner similar to aRMS Rh28 cells. This work suggests that oncogenic RAS is expressed in a context-dependent manner in RMS and may provide insight into the differential origins and therapeutic opportunities for RMS subtypes.
Identifiants
pubmed: 34389744
doi: 10.1038/s41598-021-95355-2
pii: 10.1038/s41598-021-95355-2
pmc: PMC8363632
doi:
Substances chimiques
HRAS protein, human
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
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
16505Subventions
Organisme : NICHD NIH HHS
ID : K12 HD043494
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA122706
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA231630
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
Am J Pathol. 1996 Jul;149(1):143-51
pubmed: 8686737
Cancer Res. 1998 Nov 15;58(22):5009-13
pubmed: 9823299
Cancer Res. 2007 Jul 15;67(14):6691-9
pubmed: 17638879
Cell. 2005 Feb 25;120(4):513-22
pubmed: 15734683
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):246-51
pubmed: 20018721
Ophthalmology. 1998 Aug;105(8):1442-7
pubmed: 9709755
Cancer Res. 2008 Aug 15;68(16):6587-97
pubmed: 18701482
Oncogene. 2002 Oct 7;21(45):6908-14
pubmed: 12362273
Mod Pathol. 1993 Mar;6(2):129-32
pubmed: 8483882
Cytogenet Genome Res. 2014;142(3):167-73
pubmed: 24480864
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13742-7
pubmed: 8943005
Mol Med Rep. 2019 Feb;19(2):759-770
pubmed: 30535440
Genes Cancer. 2011 Apr;2(4):466-74
pubmed: 21779514
Front Oncol. 2013 Jul 17;3:183
pubmed: 23882450
Nature. 2007 Feb 8;445(7128):661-5
pubmed: 17251932
Cancer. 1969 Sep;24(3):520-6
pubmed: 4241949
Cell. 1997 Mar 7;88(5):593-602
pubmed: 9054499
Front Oncol. 2015 Jun 22;5:131
pubmed: 26157704
Clin Cancer Res. 2011 Dec 1;17(23):7324-36
pubmed: 21948088
Oncogene. 1997 Feb 6;14(5):623-5
pubmed: 9053862
J Clin Oncol. 1990 Mar;8(3):443-52
pubmed: 2407808
Nature. 2005 Aug 4;436(7051):720-4
pubmed: 16079850
Cancer Cell. 2013 Dec 9;24(6):710-24
pubmed: 24332040
Genes Chromosomes Cancer. 1992 Nov;5(4):299-310
pubmed: 1283318
PLoS Biol. 2004 Feb;2(2):E22
pubmed: 14966529
Nature. 1986 Oct 16-22;323(6089):643-6
pubmed: 2877398
Clin Sci (Lond). 2006 May;110(5):525-41
pubmed: 16597322
Br J Cancer. 1991 Jun;63(6):879-84
pubmed: 1906291
Genes Chromosomes Cancer. 2006 Jun;45(6):583-91
pubmed: 16518851
J Biol Chem. 1996 Sep 6;271(36):21920-6
pubmed: 8702995
Cancer Res. 1989 Nov 15;49(22):6324-7
pubmed: 2680062
Genes Dev. 2013 Apr 15;27(8):900-15
pubmed: 23599344
Nature. 2001 May 17;411(6835):355-65
pubmed: 11357143
Genes Dev. 2002 Aug 15;16(16):2045-57
pubmed: 12183360
Hum Mol Genet. 2007 Feb 15;16(4):374-9
pubmed: 17164262
Sci Signal. 2017 Sep 26;10(498):
pubmed: 28951536
Cancer Res. 2018 Apr 15;78(8):2000-2013
pubmed: 29437705
Nature. 2005 Aug 4;436(7051):725-30
pubmed: 16079851
Cancer Cell. 2005 Jun;7(6):533-45
pubmed: 15950903
Cancer Res. 1987 Aug 15;47(16):4501-7
pubmed: 3607778
Expert Opin Ther Targets. 2013 May;17(5):507-31
pubmed: 23360111
Cancer Res. 2010 Jan 15;70(2):762-71
pubmed: 20068162
Nature. 2002 Jun 27;417(6892):949-54
pubmed: 12068308
Cancer. 2009 Sep 15;115(18):4218-26
pubmed: 19536876
Cancer Genet Cytogenet. 1998 Apr 1;102(1):32-9
pubmed: 9530337
Curr Biol. 1996 Dec 1;6(12):1621-7
pubmed: 8994826
Cancer Res. 2021 Jan 1;81(1):199-212
pubmed: 33168646
Cytogenet Cell Genet. 1987;45(3-4):148-55
pubmed: 3691179
Cancer Discov. 2014 Feb;4(2):216-31
pubmed: 24436047
Trends Cell Biol. 2012 Apr;22(4):211-9
pubmed: 22245068
Nat Rev Cancer. 2011 Jun 24;11(7):503-11
pubmed: 21701512
Nature. 2005 Aug 4;436(7051):660-5
pubmed: 16079837
Nature. 2005 Aug 4;436(7051):642
pubmed: 16079833
J Biol Chem. 2010 Jul 9;285(28):21625-35
pubmed: 20452986
Nat Rev Cancer. 2006 Jun;6(6):472-6
pubmed: 16723993
Nat Cell Biol. 2007 May;9(5):493-505
pubmed: 17450133
Cancers (Basel). 2020 Nov 10;12(11):
pubmed: 33182548
Semin Cancer Biol. 2011 Dec;21(6):367-76
pubmed: 22037160
Semin Cancer Biol. 2019 Feb;54:162-173
pubmed: 29518522
Cancer Res. 2005 Jun 1;65(11):4490-5
pubmed: 15930263
Genes Dev. 2014 Jul 15;28(14):1578-91
pubmed: 25030697
Oncogene. 1994 Nov;9(11):3379-87
pubmed: 7936666
Clin Cancer Res. 2012 Feb 1;18(3):748-57
pubmed: 22142829
BMC Cancer. 2011 May 30;11:211:1-11
pubmed: 21624110
Mol Cancer Res. 2013 Apr;11(4):329-38
pubmed: 23364532
Oncogene. 2016 Mar 10;35(10):1328-33
pubmed: 26028035
Curr Biol. 2006 Dec 19;16(24):2385-94
pubmed: 17174914
Leuk Lymphoma. 1992 Aug;7(5-6):359-62
pubmed: 1493437
Oncogene. 2012 Apr 12;31(15):1949-62
pubmed: 21909130
Nature. 2007 Feb 8;445(7128):656-60
pubmed: 17251933
EMBO J. 2004 Jan 14;23(1):212-20
pubmed: 14713953
Genes Dev. 1998 Oct 1;12(19):2997-3007
pubmed: 9765202
Genes Dev. 1999 Nov 15;13(22):2905-27
pubmed: 10579998
Cancer Cell. 2008 Dec 9;14(6):458-70
pubmed: 19061837
PLoS Genet. 2015 Mar 13;11(3):e1005075
pubmed: 25768946
Nat Commun. 2015 Jul 03;6:7557
pubmed: 26138366
Genes Dev. 1998 Oct 1;12(19):3008-19
pubmed: 9765203
J Clin Invest. 2014 Jan;124(1):285-96
pubmed: 24334454
Cancer Res. 2008 Dec 1;68(23):9583-8
pubmed: 19047133