Role of the CXCR4-LASP1 Axis in the Stabilization of Snail1 in Triple-Negative Breast Cancer.
A20
Akt
CXCR4
GSK-3β
LASP1
Snail1 stability
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
21 Aug 2020
21 Aug 2020
Historique:
received:
29
06
2020
revised:
08
08
2020
accepted:
14
08
2020
entrez:
23
8
2020
pubmed:
23
8
2020
medline:
23
8
2020
Statut:
epublish
Résumé
The CXCL12-CXCR4 axis plays a vital role in many steps of breast cancer metastasis, but the molecular mechanisms have not been fully elucidated. We previously reported that activation of CXCR4 by CXCL12 promotes the nuclear localization of LASP1 (LIM and SH3 protein 1). The nuclear LASP1 then interacts with Snail1 in triple-negative breast cancer (TNBC) cell lines. In this study, we report that the nuclear accumulation and retention of Snail1 was dependent on an increase in nuclear LASP1 levels driven by active CXCR4. The CXCR4-LASP1 axis may directly regulate the stabilization of nuclear Snail1, by upregulating nuclear levels of pS473-Akt, pS9-GSK-3β, A20, and LSD1. Furthermore, the activation of CXCR4 induced association of LASP1 with Snail1, A20, GSK-3β, and LSD1 endogenously. Thus, nuclear LASP1 may also regulate protein-protein interactions that facilitate the stability of Snail1. Genetic ablation of LASP1 resulted in the mislocalization of nuclear Snail1, loss of the ability of TNBC cells to invade Matrigel and a dysregulated expression of both epithelial and mesenchymal markers, including an increased expression of ALDH1A1, a marker for epithelial breast cancer stem-like cells. Our findings reveal a novel role for the CXCR4-LASP1 axis in facilitating the stability of nuclear localized Snail1.
Identifiants
pubmed: 32825729
pii: cancers12092372
doi: 10.3390/cancers12092372
pmc: PMC7563118
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : R21 CA202176
Pays : United States
Organisme : NIH HHS
ID : R21CA202176 (to DR)
Pays : United States
Organisme : University of Toledo
ID : startup grants (F110796 to DR)
Organisme : Ohio Cancer Research
ID : 2017
Références
Gene. 2000 Oct 17;257(1):1-12
pubmed: 11054563
Neoplasia. 2019 Apr;21(4):413-427
pubmed: 30925417
Cancer Res. 2013 Jan 1;73(1):235-45
pubmed: 23054398
Cancer Res. 2006 Jun 1;66(11):5665-75
pubmed: 16740704
Cancer Cell. 2014 Sep 8;26(3):358-373
pubmed: 25203322
EMBO J. 2010 Jun 2;29(11):1803-16
pubmed: 20389281
Nat Cell Biol. 2000 Feb;2(2):84-9
pubmed: 10655587
Nat Cell Biol. 2006 Dec;8(12):1398-406
pubmed: 17072303
Oncogene. 2010 Sep 2;29(35):4896-904
pubmed: 20562920
Methods Enzymol. 2009;460:315-30
pubmed: 19446732
PLoS One. 2010 Apr 19;5(4):e10050
pubmed: 20419088
Contrib Microbiol. 2006;13:191-199
pubmed: 16627966
Nat Protoc. 2006;1(1):179-85
pubmed: 17406230
J Biol Chem. 2003 May 2;278(18):15601-7
pubmed: 12571245
Cancer Cell. 2013 Mar 18;23(3):316-31
pubmed: 23453623
Oncogene. 2016 Mar 3;35(9):1122-33
pubmed: 25982273
Breast Cancer Res. 2010;12(3):206
pubmed: 20594364
Nat Commun. 2017 Jan 09;8:13923
pubmed: 28067227
Proc Natl Acad Sci U S A. 2019 Apr 9;116(15):7353-7362
pubmed: 30910979
Cell Cycle. 2014;13(11):1708-16
pubmed: 24675890
Breast Cancer Res Treat. 2019 Apr;174(2):413-422
pubmed: 30594967
Oncotarget. 2016 Sep 27;7(39):64244-64259
pubmed: 27588391
PLoS One. 2013;8(2):e56664
pubmed: 23431386
Oncotarget. 2015 Jan 20;6(2):1020-30
pubmed: 25544759
Biomaterials. 2020 Apr;238:119853
pubmed: 32062146
Nat Cell Biol. 2016 Nov;18(11):1221-1232
pubmed: 27749822
Nat Cell Biol. 2017 Oct;19(10):1260-1273
pubmed: 28892081
Cold Spring Harb Symp Quant Biol. 2016;81:11-19
pubmed: 28057845
CA Cancer J Clin. 2019 Jan;69(1):7-34
pubmed: 30620402
Nat Rev Mol Cell Biol. 2019 Feb;20(2):69-84
pubmed: 30459476
Sci Rep. 2016 Jun 23;6:28587
pubmed: 27335258
J Pathol. 2004 Jun;203(2):661-71
pubmed: 15141381
Curr Pharm Des. 2014;20(11):1698-705
pubmed: 23888971
Biochem Biophys Res Commun. 2009 Oct 16;388(2):199-204
pubmed: 19660434
Nat Rev Cancer. 2018 Feb;18(2):128-134
pubmed: 29326430
Hum Pathol. 2011 Aug;42(8):1125-31
pubmed: 21315410
Nat Med. 2011 Mar;17(3):313-9
pubmed: 21386835
Breast Cancer Res Treat. 2010 Oct;123(3):725-31
pubmed: 20020197
Front Oncol. 2019 Apr 24;9:284
pubmed: 31106142
Cancer Res. 2007 Dec 15;67(24):11721-31
pubmed: 18089802
Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G37-G44
pubmed: 18483181
J Clin Invest. 2012 Apr;122(4):1469-86
pubmed: 22406531
Front Oncol. 2019 Dec 06;9:1311
pubmed: 31867270
Clin Cancer Res. 2018 Apr 15;24(8):1845-1852
pubmed: 29378733
Oncoimmunology. 2012 Dec 1;1(9):1484-1494
pubmed: 23264895
J Coll Physicians Surg Pak. 2019 Mar;29(3):240-244
pubmed: 30823950
PLoS One. 2019 Aug 26;14(8):e0221721
pubmed: 31449546
Tumour Biol. 2015 Jun;36(6):4565-73
pubmed: 25608841
Nat Rev Cancer. 2013 Feb;13(2):97-110
pubmed: 23344542
Cancer Res. 2011 Jan 15;71(2):603-13
pubmed: 21123450
Mol Cell Biol. 2003 Jul;23(14):5078-89
pubmed: 12832491
Mol Cell Biol. 2015 Dec 28;36(6):923-40
pubmed: 26711268
Cells. 2020 Feb 14;9(2):
pubmed: 32075106
Cancer Res. 2005 Apr 15;65(8):3179-84
pubmed: 15833848
Oncogenesis. 2018 Mar 29;7(3):32
pubmed: 29593211
Clin Transl Med. 2014 Dec;3(1):28
pubmed: 26932374
Front Oncol. 2018 Sep 21;8:391
pubmed: 30298118
Nat Cell Biol. 2004 Oct;6(10):931-40
pubmed: 15448698
Thromb Haemost. 2009 Sep;102(3):520-8
pubmed: 19718473
Adv Radiat Oncol. 2017 Feb 07;2(2):105-109
pubmed: 28740920
Br J Cancer. 2010 May 25;102(11):1645-53
pubmed: 20461080
Cancer Res. 2016 Nov 1;76(21):6205-6217
pubmed: 27503928
J Clin Invest. 1996 Oct 1;98(7):1544-9
pubmed: 8833902
Nat Rev Immunol. 2011 Aug 25;11(9):597-606
pubmed: 21866172
Cancer Cell. 2005 Sep;8(3):197-209
pubmed: 16169465
Nature. 2001 Mar 1;410(6824):50-6
pubmed: 11242036
Development. 2002 Apr;129(7):1785-93
pubmed: 11923213
Mol Cancer Res. 2011 Aug;9(8):997-1007
pubmed: 21665936
Semin Cancer Biol. 2016 Feb;36:71-9
pubmed: 26506454
J Clin Oncol. 2008 Mar 10;26(8):1275-81
pubmed: 18250347
BMC Cancer. 2011 Sep 19;11:396
pubmed: 21929801