Phosphorylation of the proline-rich domain of WAVE3 drives its oncogenic activity in breast cancer.
Animals
Carcinogenesis
/ metabolism
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Female
Humans
Mice
Phosphorylation
Platelet-Derived Growth Factor
/ metabolism
Proline-Rich Protein Domains
Protein-Tyrosine Kinases
/ metabolism
Stem Cell Niche
Triple Negative Breast Neoplasms
/ metabolism
Wiskott-Aldrich Syndrome Protein Family
/ metabolism
Y-Box-Binding Protein 1
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 02 2021
16 02 2021
Historique:
received:
28
09
2020
accepted:
03
02
2021
entrez:
17
2
2021
pubmed:
18
2
2021
medline:
4
1
2022
Statut:
epublish
Résumé
Post-translational modification of proteins, such as tyrosine phosphorylation, plays a major role in driving the oncogenic activity of oncogenes. WAVE3 (WASF3), an adaptor and actin cytoskeleton remodeling protein, contributes to cell migration, cancer cell invasion, and metastasis. WAVE3 plays a vital role in the progression and metastasis of triple negative breast cancer (TNBC), in part through the regulation of cancer stem cells (CSCs). Several studies have shown that WAVE3 tyrosine phosphorylation is required for its oncogenic activity. Moreover, our recent study showed that the proline rich domain (PRD) of WAVE3 is required for maintenance of the CSC niche in breast cancer by regulating the nuclear translocation of the CSC-specific nuclear transcription factor YB1. Here, we show that the PRD domain of WAVE3 and its phosphorylation are essential for driving the oncogenic activity of WAVE3. We show that phosphorylation of WAVE3 PRD is essential for migration and invasion of breast cancer cells in vitro, as well as tumor growth and metastasis in vivo. Mechanistically, we show that phosphorylation of the WAVE3 PRD is essential for interaction between WAVE3 and YB1. Loss of PRD phosphorylation inhibits such interaction and the YB1-mediated activation of expression of CSC markers, as well as the WAVE3 mediated activation of EMT. Together, our study identifies a novel role of WAVE3 and its PRD domain in the regulation of the invasion metastasis cascade in BC that is independent of the known function of WAVE3 as an actin cytoskeleton remodeling protein through the WAVE regulatory complex (WRC).
Identifiants
pubmed: 33594155
doi: 10.1038/s41598-021-83479-4
pii: 10.1038/s41598-021-83479-4
pmc: PMC7887190
doi:
Substances chimiques
Platelet-Derived Growth Factor
0
WASF3 protein, human
0
Wasf3 protein, mouse
0
Wiskott-Aldrich Syndrome Protein Family
0
Y-Box-Binding Protein 1
0
Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3868Subventions
Organisme : NCI NIH HHS
ID : R01 CA226921
Pays : United States
Commentaires et corrections
Type : ErratumIn
Références
N Engl J Med. 2019 May 16;380(20):1929-1940
pubmed: 31091374
Am J Pathol. 2007 Jun;170(6):2112-21
pubmed: 17525277
Cell. 2014 Jan 16;156(1-2):195-207
pubmed: 24439376
Curr Biol. 1996 Aug 1;6(8):981-8
pubmed: 8805332
J Biol Chem. 2009 Nov 27;284(48):33019-29
pubmed: 19801681
Mol Cell Biol. 2006 Jan;26(1):277-92
pubmed: 16354698
Nature. 2000 Dec 7;408(6813):732-5
pubmed: 11130076
Int J Cancer. 2012 Sep 15;131(6):E905-15
pubmed: 22581642
J Biol Chem. 2005 Jun 10;280(23):21748-55
pubmed: 15826941
Cancer Res. 2017 Sep 15;77(18):5129-5141
pubmed: 28687620
Breast Cancer Res Treat. 2013 Nov;142(2):341-53
pubmed: 24197660
Ann Transl Med. 2020 Jul;8(14):900
pubmed: 32793744
Stem Cell Res Ther. 2019 Aug 2;10(1):233
pubmed: 31375149
Exp Cell Res. 2005 Aug 1;308(1):135-45
pubmed: 15907837
Oncogene. 2014 Jan 9;33(2):203-11
pubmed: 23318438
Int J Cancer. 2011 Dec 15;129(12):2825-35
pubmed: 21544801
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4379-83
pubmed: 15070726
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Genome Biol. 2009;10(6):226
pubmed: 19589182
Int J Cancer. 2011 Sep 15;129(6):1331-43
pubmed: 21105030
Int Rev Cytol. 2003;229:245-86
pubmed: 14669958
Nat Cell Biol. 2004 Apr;6(4):319-27
pubmed: 15048123
J Biol Chem. 2007 Sep 7;282(36):26257-65
pubmed: 17623672
Oncogenesis. 2020 Oct 5;9(10):87
pubmed: 33012785
BMC Cancer. 2013 Oct 04;13:453
pubmed: 24089705
Nat Rev Cancer. 2003 Jun;3(6):453-8
pubmed: 12778135
Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14449-54
pubmed: 21844371
Semin Cell Dev Biol. 2013 Apr;24(4):287-97
pubmed: 23116924
Biochemistry (Mosc). 2011 Dec;76(13):1402-33
pubmed: 22339596
PLoS One. 2012;7(8):e42895
pubmed: 22952619
Oncotarget. 2017 Oct 24;8(61):104072-104089
pubmed: 29262622
RNA Biol. 2008 Jul-Sep;5(3):115-9
pubmed: 19182522
Sci Rep. 2018 May 9;8(1):7360
pubmed: 29743493
EMBO Rep. 2008 Jun;9(6):582-9
pubmed: 18483486
Oncogene. 2005 Feb 17;24(8):1309-19
pubmed: 15608687
EMBO J. 1998 Dec 1;17(23):6932-41
pubmed: 9843499
EMBO J. 1996 Oct 1;15(19):5326-35
pubmed: 8895577
J Biol Chem. 2012 Mar 23;287(13):10051-10059
pubmed: 22315230
Cell Cycle. 2008 Oct;7(20):3112-8
pubmed: 18927505
Ann Transl Med. 2020 Jul;8(14):899
pubmed: 32793743
EMBO J. 1990 Oct;9(10):3279-86
pubmed: 2170111
Mamm Genome. 2003 May;14(5):314-22
pubmed: 12856283
Oncogene. 2002 Aug 29;21(38):5967-74
pubmed: 12185600
Br J Cancer. 2010 Sep 28;103(7):1066-75
pubmed: 20717117
Carcinogenesis. 2013 Sep;34(9):1994-9
pubmed: 23677069
JAKSTAT. 2015 Feb 03;3(4):e1009276
pubmed: 26413422
FASEB J. 2014 May;28(5):2260-71
pubmed: 24469992
Biochem Biophys Res Commun. 1999 Jun 24;260(1):296-302
pubmed: 10381382
Cell. 2000 Jan 7;100(1):57-70
pubmed: 10647931
Nat Cell Biol. 2008 May;10(5):593-601
pubmed: 18376396
PLoS One. 2014 Oct 16;9(10):e110627
pubmed: 25329315
Bioessays. 2003 Jul;25(7):691-8
pubmed: 12815724
J Biol Chem. 2008 May 30;283(22):14910-4
pubmed: 18411277
BMC Cancer. 2014 May 09;14:328
pubmed: 24885403
J Cell Sci. 2001 May;114(Pt 10):1801-9
pubmed: 11329366
J Biol Chem. 1999 Sep 24;274(39):27605-9
pubmed: 10488099
Cell. 2006 Nov 17;127(4):679-95
pubmed: 17110329