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Despite recent evidence that links the S1P receptor 1 (S1P1) to TNBC cell survival, its role in TNBC invasion and the underlying mechanisms remain elusive. Combining analyses of human TNBC cells with zebrafish xenografts, we found that phosphorylation of S1P receptor 1 (S1P1) at threonine 236 (T236) is critical for TNBC dissemination. Compared to luminal breast cancer cells, TNBC cells exhibit a significant increase of phospho-S1P1 T236 but not the total S1P1 levels. Misexpression of phosphorylation-defective S1P1 T236A (alanine) decreases TNBC cell migration in vitro and disease invasion in zebrafish xenografts. Pharmacologic disruption of S1P1 T236 phosphorylation, using either a pan-AKT inhibitor (MK2206) or an S1P1 functional antagonist (FTY720, an FDA-approved drug for treating multiple sclerosis), suppresses TNBC cell migration in vitro and tumor invasion in vivo. Finally, we show that human TNBC cells with AKT activation and elevated phospho-S1P1 T236 are sensitive to FTY720-induced cytotoxic effects. These findings indicate that the AKT-enhanced phosphorylation of S1P1 T236 mediates much of the TNBC invasiveness, providing a potential biomarker to select TNBC patients for the clinical application of FTY720.<\/jats:p>","DOI":"10.3390\/cells12070980","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T04:31:05Z","timestamp":1679632265000},"page":"980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["S1P1 Threonine 236 Phosphorylation Mediates the Invasiveness of Triple-Negative Breast Cancer and Sensitivity to FTY720"],"prefix":"10.3390","volume":"12","author":[{"given":"Fabrice J. 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Khuan","family":"Wong","sequence":"additional","affiliation":[{"name":"Biomedical Genetics Section, Department of Medicine, Department of Pathology and Laboratory Medicine, Genetics and Genomics Graduate Program, Cancer Center, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J.","family":"Quinton","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine, Section of Hematology and Medical Oncology, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4053-6067","authenticated-orcid":false,"given":"Jason N.","family":"Berman","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Departments of Pediatrics and Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON 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Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9308","DOI":"10.1016\/S0021-9258(19)38849-0","article-title":"An abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G-protein-coupled receptors","volume":"265","author":"Hla","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/S1097-2765(01)00324-0","article-title":"Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis","volume":"8","author":"Lee","year":"2001","journal-title":"Mol. 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Invest."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.canlet.2008.11.025","article-title":"S1P\/S1P1 signaling stimulates cell migration and invasion in Wilms tumor","volume":"276","author":"Li","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1476-4598-5-69","article-title":"Tumor cell invasion of collagen matrices requires coordinate lipid agonist-induced G-protein and membrane-type matrix metalloproteinase-I-dependent signaling","volume":"5","author":"Fisher","year":"2006","journal-title":"Mol. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1158\/1541-7786.MCR-08-0061","article-title":"Sphingosine-1-phosphate regulates glioblastoma cell invasiveness through the urokinase plasminogen activator system and CCN1\/Cry61","volume":"7","author":"Young","year":"2009","journal-title":"Mol. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1172\/JCI200422716","article-title":"Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference","volume":"114","author":"Chae","year":"2004","journal-title":"J. Clin. Invest."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.2353\/ajpath.2010.100220","article-title":"High expression of sphingosine 1-phosphate receptors, S1P1 and S1P3, sphingosine kinase 1, and extracellular signal-regulated kinase-1\/2 is associated with development of tamoxifen resistance in estrogen receptor-positive breast cancer patients","volume":"177","author":"Watson","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12951-021-00904-6","article-title":"The targetable nanoparticle BAF312@cRGD-CaP-NP represses tumor growth and angiogenesis by downregulating the S1PR1\/P-STAT3\/VEGFA axis in triple-negative breast cancer","volume":"19","author":"Gong","year":"2021","journal-title":"J. Nanobiotechnology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"529962","DOI":"10.3389\/fphar.2020.529962","article-title":"Coix Seed Oil Exerts an Anti-Triple-Negative Breast Cancer Effect by Disrupting miR-205\/S1PR1 Axis","volume":"11","author":"Fang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0140-6736(05)17947-1","article-title":"Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer","volume":"365","author":"Wang","year":"2005","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1475-2867-9-7","article-title":"Increasingly transformed MCF-10A cells have a progressively tumor-like phenotype in three-dimensional basement membrane culture","volume":"9","author":"Imbalzano","year":"2009","journal-title":"Cancer Cell Int."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Teng, Y., Xie, X., Walker, S., White, D.T., Mumm, J.S., and Cowell, J.K. (2013). Evaluating human cancer cell metastasis in zebrafish. 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Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/nature08021","article-title":"Genes that mediate breast cancer metastasis to the brain","volume":"459","author":"Bos","year":"2009","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5816","DOI":"10.1158\/1078-0432.CCR-12-1141","article-title":"Biomarkers of response to Akt inhibitor MK-2206 in breast cancer","volume":"18","author":"Sangai","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23106","DOI":"10.18632\/oncotarget.7145","article-title":"The emerging role of FTY720 (Fingolimod) in cancer treatment","volume":"7","author":"White","year":"2016","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/WNF.0b013e3181cbf825","article-title":"Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis","volume":"33","author":"Chun","year":"2010","journal-title":"Clin. Neuropharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.cell.2007.06.009","article-title":"AKT\/PKB signaling: Navigating downstream","volume":"129","author":"Manning","year":"2007","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1158\/2326-6066.CIR-13-0127","article-title":"PD-L1 expression in triple negative breast cancer","volume":"2","author":"Mittendorf","year":"2014","journal-title":"Cancer Immunol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/his.12313","article-title":"Investigation of molecular alterations of AKT-3 in triple-negative breast cancer","volume":"64","author":"Daly","year":"2014","journal-title":"Histopathology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6377","DOI":"10.1016\/j.bmcl.2013.09.058","article-title":"Modulators of the Sphingosine 1-phosphate receptor 1","volume":"23","author":"Urbano","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/labinvest.2013.7","article-title":"Sphingosine-1-phosphate receptor 1 in classical hodgkin lymphoma: Assessment of expression and role in cell migration","volume":"93","author":"Kluk","year":"2013","journal-title":"Lab. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/ijc.29362","article-title":"Sphingosine kinase 1 as a potential therapeutic target in epithelial ovarian cancer","volume":"137","author":"Lee","year":"2015","journal-title":"Int. J. 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