title: Snail1, Snail2, and E47 promote mammary epithelial branching morphogenesis.
abstract: Several E-box-binding transcription factors regulate individual and collective cell migration and enhance the motility of epithelial cells by promoting epithelial-mesenchymal transition (EMT). Here, we characterized the role of a subset of these transcription factors and the EMT proteome in branching morphogenesis of mammary epithelial tissues using a three-dimensional organotypic culture model of the mammary duct. We found that the transcription factors Snail1, Snail2, and E47 were transiently upregulated at branch sites; decreasing the expression of these transcription factors inhibited branching. Conversely, ectopic expression of Snail1, Snail2, and E47 induced branching in the absence of exogenous stimuli. These changes correlated with the expression of mesenchymal markers and repression of E-cadherin, which was essential for branching. Snail1 and Snail2 also promoted cell survival at branch sites, but this was not sufficient to induce branching. These findings indicate that Snail1, Snail2, and E47 can promote collective migration during branching morphogenesis of mammary epithelial tissues through key regulators of EMT.
authors: Departments of Chemical & Biological Engineering and Molecular Biology, Princeton University, Princeton, NJ, USA.
authors: Kangae
authors: K
authors: Lee
authors: Nikolce
authors: N
authors: Gjorevski
authors: Eline
authors: E
authors: Boghaert
authors: Derek C
authors: DC
authors: Radisky
authors: Celeste M
authors: CM
authors: Nelson
references: Breast Cancer Res. 2006;8(1):201
references: 16524451
references: Science. 2010 Jul 30;329(5991):562-5
references: 20671187
references: Mol Cell Biol. 2004 Sep;24(17):7559-66
references: 15314165
references: J Cell Biochem. 2010 May;110(1):44-51
references: 20336666
references: J Biol Chem. 2001 Jul 20;276(29):27424-31
references: 11309385
references: Dev Biol. 2004 Nov 15;275(2):325-42
references: 15501222
references: Nat Rev Cancer. 2007 Jun;7(6):415-28
references: 17508028
references: Genes Dev. 2004 May 15;18(10):1131-43
references: 15155580
references: Mol Cell. 2001 Jun;7(6):1267-78
references: 11430829
references: J Clin Invest. 2009 Jun;119(6):1420-8
references: 19487818
references: J Cell Biol. 1995 Dec;131(6 Pt 1):1573-86
references: 8522613
references: J Biol Chem. 2003 Jun 6;278(23):21113-23
references: 12665527
references: Integr Biol (Camb). 2010 Nov;2(11-12):568-74
references: 20886167
references: Integr Biol (Camb). 2010 Sep;2(9):424-34
references: 20717570
references: Dev Cell. 2008 Apr;14(4):570-81
references: 18410732
references: J Biol Chem. 1997 Apr 11;272(15):9677-82
references: 9092497
references: Nat Rev Mol Cell Biol. 2002 Jul;3(7):531-7
references: 12094219
references: Development. 2004 Dec;131(24):6141-51
references: 15548586
references: Nat Rev Mol Cell Biol. 2009 Jul;10(7):445-57
references: 19546857
references: Genes Dev. 1995 Mar 15;9(6):686-99
references: 7729687
references: J Mammary Gland Biol Neoplasia. 2004 Apr;9(2):183-93
references: 15300012
references: Dev Biol. 2010 May 1;341(1):20-33
references: 19914236
references: Nat Rev Mol Cell Biol. 2005 Aug;6(8):622-34
references: 16025097
references: J Cell Sci. 2006 Aug 15;119(Pt 16):3376-84
references: 16882689
references: Dev Cell. 2009 Aug;17(2):199-209
references: 19686681
references: J Cell Biol. 1989 Mar;108(3):1127-38
references: 2466037
references: Dev Dyn. 2006 Dec;235(12):3404-12
references: 17039550
references: Science. 2006 Oct 13;314(5797):298-300
references: 17038622
references: Dev Dyn. 1992 Dec;195(4):290-302
references: 1304824
references: Dev Biol. 2008 Feb 1;314(1):224-35
references: 18177852
references: J Clin Invest. 2009 Jun;119(6):1429-37
references: 19487819
references: Mol Cell Biol. 2001 Dec;21(23):8184-8
references: 11689706
references: Dev Biol. 2007 Jun 1;306(1):193-207
references: 17448457
references: Dev Biol. 1998 Dec 1;204(1):64-79
references: 9851843
references: J Biol Chem. 2009 Mar 13;284(11):6877-84
references: 19129200
references: Nat Protoc. 2008;3(4):674-8
references: 18388950
references: Oncogene. 2008 Nov 24;27(55):6958-69
references: 19029937
references: Nat Cell Biol. 2000 Feb;2(2):76-83
references: 10655586
references: Curr Opin Cell Biol. 2010 Oct;22(5):640-50
references: 20832275
references: Semin Cancer Biol. 2005 Oct;15(5):342-52
references: 15963732
references: Development. 2005 Jul;132(14):3151-61
references: 15983400
references: J Clin Invest. 2003 Dec;112(12):1776-84
references: 14679171
references: J Cell Biol. 1998 Jan 12;140(1):159-69
references: 9425164
references: Eur Urol. 2001 Feb;39(2):222-31
references: 11223684
references: Mol Biol Cell. 2007 May;18(5):1943-52
references: 17344479
references: Cell. 2004 Jun 25;117(7):927-39
references: 15210113
references: Curr Opin Genet Dev. 2009 Aug;19(4):338-42
references: 19464162
references: Methods Mol Biol. 2011;671:107-16
references: 20967625
references: Nature. 2003 Jun 19;423(6942):876-81
references: 12815434
references: Science. 2005 Feb 18;307(5712):1098-101
references: 15718470
references: J Mammary Gland Biol Neoplasia. 2010 Jun;15(2):117-34
references: 20490631
references: Development. 2001 Aug;128(16):3117-31
references: 11688561
references: J Cell Sci. 2009 Sep 15;122(Pt 18):3203-8
references: 19726629