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REVIEW

SLUG: Critical regulator of epithelial cell identity in breast development and cancer

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Pages 578-587 | Received 18 Jun 2014, Accepted 09 Aug 2014, Published online: 26 Jan 2015

References

  • Hemavathy K, Ashraf SI, Ip YT. Snail/slug family of repressors: Slowly going into the fast lane of development and cancer. Gene 2000; 257:1-12; PMID:11054563; http://dx.doi.org/ S0378-1119(00)00371-1 [pii]
  • Nieto MA. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol 2002; 3:155-66; PMID:11994736; http://dx.doi.org/10.1038/nrm757
  • Hemavathy K, Guru SC, Harris J, Chen JD, Ip YT. Human slug is a repressor that localizes to sites of active transcription. Mol Cell Biol 2000; 20:5087-95; PMID:10866665
  • Isaac A, Sargent MG, Cooke J. Control of vertebrate left-right asymmetry by a snail-related zinc finger gene. Science 1997; 275:1301-4; PMID:9036854
  • Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T, Look AT. SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein. Mol Cell 1999; 4:343-52; PMID:10518215
  • Vega S, Morales AV, Ocana OH, Valdes F, Fabregat I, Nieto MA. Snail blocks the cell cycle and confers resistance to cell death. Genes Dev 2004; 18:1131-43; PMID:15155580; http://dx.doi.org/10.1101/gad.294104
  • Boutet A, De Frutos CA, Maxwell PH, Mayol MJ, Romero J, Nieto MA. Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney. EMBO J 2006; 25:5603-13; PMID:17093497; http://dx.doi.org/ 7601421 [pii]
  • Martinez-Alvarez C, Blanco MJ, Perez R, Rabadan MA, Aparicio M, Resel E, Martinez T, Nieto MA. Snail family members and cell survival in physiological and pathological cleft palates. Dev Biol 2004; 265:207-18; PMID:14697364; http://dx.doi.org/ S0012160603005748 [pii]
  • Kajita M, McClinic KN, Wade PA. Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress. Mol Cell Biol 2004; 24:7559-66; PMID:15314165; http://dx.doi.org/10.1128/MCB.24.17.7559-7566.2004
  • Barrallo-Gimeno A, Nieto MA. The snail genes as inducers of cell movement and survival: Implications in development and cancer. Development 2005; 132:3151-61; PMID:15983400; http://dx.doi.org/ 132/14/3151 [pii]
  • Dhasarathy A, Phadke D, Mav D, Shah RR, Wade PA. The transcription factors snail and slug activate the transforming growth factor-beta signaling pathway in breast cancer. PLoS One 2011; 6:e26514; PMID:22028892; http://dx.doi.org/10.1371/journal.pone.0026514
  • Kurrey NKKA, Bapat SA. Snail and slug are major determinants of ovarian cancer invasiveness at the transcription level. Gynecol Oncol 2005; 97:155-65; PMID:15790452; http://dx.doi.org/ S0090-8258(04)01058-3 [pii]
  • Uygur B, Wu WS. SLUG promotes prostate cancer cell migration and invasion via CXCR4/CXCL12 axis. Mol Cancer 2011; 10:139,4598-10-139; PMID:22074556; http://dx.doi.org/10.1186/1476-4598-10-139 [doi]
  • Turner FE, Broad S, Khanim FL, Jeanes A, Talma S, Hughes S, Tselepis C, Hotchin NA. Slug regulates integrin expression and cell proliferation in human epidermal keratinocytes. J Biol Chem 2006; 281:21321-31; PMID:16707493; http://dx.doi.org/ M509731200 [pii]
  • Emadi Baygi M, Soheili ZS, Essmann F, Deezagi A, Engers R, Goering W, Schulz WA. Slug/SNAI2 regulates cell proliferation and invasiveness of metastatic prostate cancer cell lines. Tumour Biol 2010; 31:297-307; PMID:20506051; http://dx.doi.org/10.1007/s13277-010-0037-5
  • Cobaleda C, Perez-Caro M, Vicente-Duenas C, Sanchez-Garcia I. Function of the zinc-finger transcription factor SNAI2 in cancer and development. Annu Rev Genet 2007; 41:41-61; PMID:17550342; http://dx.doi.org/10.1146/annurev.genet.41.110306.130146
  • Shirley SH, Hudson LG, He J, Kusewitt DF. The skinny on slug. Mol Carcinog 2010; 49:851-61; PMID:20721976; http://dx.doi.org/10.1002/mc.20674.
  • Grimes HL, Chan TO, Zweidler-McKay PA, Tong B, Tsichlis PN. The gfi-1 proto-oncoprotein contains a novel transcriptional repressor domain, SNAG, and inhibits G1 arrest induced by interleukin-2 withdrawal. Mol Cell Biol 1996; 16:6263-72; PMID:8887656
  • Chiang C, Ayyanathan K. Snail/gfi-1 (SNAG) family zinc finger proteins in transcription regulation, chromatin dynamics, cell signaling, development, and disease. Cytokine Growth Factor Rev 2013; 24:123-31; PMID:23102646; http://dx.doi.org/10.1016/j.cytogfr.2012.09.002.
  • Sefton M, Sanchez S, Nieto MA. Conserved and divergent roles for members of the snail family of transcription factors in the chick and mouse embryo. Development 1998; 125:3111-21; PMID:9671584
  • Molina-Ortiz P, Villarejo A, MacPherson M, Santos V, Montes A, Souchelnytskyi S, Portillo F, Cano A. Characterization of the SNAG and SLUG domains of Snail2 in the repression of E-cadherin and EMT induction: Modulation by serine 4 phosphorylation. PLoS One 2012; 7:e36132; PMID:22567133; http://dx.doi.org/10.1371/journal.pone.0036132.
  • Jiang R, Lan Y, Norton CR, Sundberg JP, Gridley T. The slug gene is not essential for mesoderm or neural crest development in mice. Dev Biol 1998; 198:277-85; PMID:9659933
  • Carver EA, Jiang R, Lan Y, Oram KF, Gridley T. The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol Cell Biol 2001; 21:8184-8; PMID:11689706; http://dx.doi.org/10.1128/MCB.21.23.8184-8188.2001 [doi]
  • Moreno-Bueno G, Cubillo E, Sarrio D, Peinado H, Rodriguez-Pinilla SM, Villa S, Bolos V, Jorda M, Fabra A, Portillo F, et al. Genetic profiling of epithelial cells expressing E-cadherin repressors reveals a distinct role for snail, slug, and E47 factors in epithelial-mesenchymal transition. Cancer Res 2006; 66:9543-56; PMID:17018611; http://dx.doi.org/10.1158/0008-5472.CAN-06-0479
  • Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M, Cano A. The transcription factor slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: A comparison with snail and E47 repressors. J Cell Sci 2003; 116:499-511; PMID:12508111
  • Gras B, Jacqueroud L, Wierinckx A, Lamblot C, Fauvet F, Lachuer J, Puisieux A, Ansieau S. Snail family members unequally trigger EMT and thereby differ in their ability to promote the neoplastic transformation of mammary epithelial cells. PLoS One 2014; 9:e92254; PMID:24638100; http://dx.doi.org/10.1371/journal.pone.0092254 [doi]
  • Villarejo A, Cortes-Cabrera A, Molina-Ortiz P, Portillo F, Cano A. Differential role of Snail1 and Snail2 zinc fingers in E-cadherin repression and epithelial to mesenchymal transition. J Biol Chem 2014; 289:930-41; PMID:24297167; http://dx.doi.org/10.1074/jbc.M113.528026
  • Come C, Magnino F, Bibeau F, De Santa Barbara P, Becker KF, Theillet C, Savagner P. Snail and slug play distinct roles during breast carcinoma progression. Clin Cancer Res 2006; 12:5395-402; PMID:17000672; http://dx.doi.org/10.1158/1078-0432.CCR-06-0478
  • Visvader JE. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes Dev 2009; 23:2563-77; PMID:19933147; http://dx.doi.org/10.1101/gad.1849509
  • Smalley MJ, Titley J, Paterson H, Perusinghe N, Clarke C, O’Hare MJ. Differentiation of separated mouse mammary luminal epithelial and myoepithelial cells cultured on EHS matrix analyzed by indirect immunofluorescence of cytoskeletal antigens. J Histochem Cytochem 1999; 47:1513-24; PMID:10567435
  • Warburton MJ, Mitchell D, Ormerod EJ, Rudland P. Distribution of myoepithelial cells and basement membrane proteins in the resting, pregnant, lactating, and involuting rat mammary gland. J Histochem Cytochem 1982; 30:667-76; PMID:6179984
  • Dairkee S, Heid HW. Cytokeratin profile of immunomagnetically separated epithelial subsets of the human mammary gland. In Vitro Cell Dev Biol Anim 1993; 29A:427-32; PMID:7686143
  • Gudjonsson T, Adriance MC, Sternlicht MD, Petersen OW, Bissell MJ. Myoepithelial cells: Their origin and function in breast morphogenesis and neoplasia. J Mammary Gland Biol Neoplasia 2005; 10:261-72; PMID:16807805; http://dx.doi.org/10.1007/s10911-005-9586-4
  • Sopel M. The myoepithelial cell: Its role in normal mammary glands and breast cancer. Folia Morphol (Warsz) 2010; 69:1-14; PMID:20235044
  • Jeselsohn R, Brown NE, Arendt L, Klebba I, Hu MG, Kuperwasser C, Hinds PW. Cyclin D1 kinase activity is required for the self-renewal of mammary stem and progenitor cells that are targets of MMTV-ErbB2 tumorigenesis. Cancer Cell 2010; 17:65-76; PMID:20129248; http://dx.doi.org/10.1016/j.ccr.2009.11.024
  • Shehata M, Teschendorff A, Sharp G, Novcic N, Russell A, Avril S, Prater M, Eirew P, Caldas C, Watson CJ, et al. Phenotypic and functional characterization of the luminal cell hierarchy of the mammary gland. Breast Cancer Res 2012; 14:R134; PMID:23088371; http://dx.doi.org/10.1186/bcr/3334
  • Kittrell FS, Carletti MZ, Kerbawy S, Heestand J, Xian W, Zhang M, Lamarca HL, Sonnenberg A, Rosen JM, Medina D, et al. Prospective isolation and characterization of committed and multipotent progenitors from immortalized mouse mammary epithelial cells with morphogenic potential. Breast Cancer Res 2011; 13:R41; PMID:21466693; http://dx.doi.org/10.1186/bcr2863
  • Van Keymeulen A, Rocha AS, Ousset M, Beck B, Bouvencourt G, Rock J, Sharma N, Dekoninck S, Blanpain C. Distinct stem cells contribute to mammary gland development and maintenance. Nature 2011; 479:189-93; PMID:21983963; http://dx.doi.org/10.1038/nature10573
  • dos Santos CO, Rebbeck C, Rozhkova E, Valentine A, Samuels A, Kadiri LR, Osten P, Harris EY, Uren PJ, Smith AD, et al. Molecular hierarchy of mammary differentiation yields refined markers of mammary stem cells. Proc Natl Acad Sci U S A 2013; 110:7123-30; PMID:23580620; http://dx.doi.org/10.1073/pnas.1303919110
  • Asselin-Labat ML, Sutherland KD, Barker H, Thomas R, Shackleton M, Forrest NC, Hartley L, Robb L, Grosveld FG, van der Wees J, et al. Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nat Cell Biol 2007; 9:201-9; PMID:17187062; http://dx.doi.org/10.1038/ncb1530
  • Eirew P, Stingl J, Raouf A, Turashvili G, Aparicio S, Emerman JT, Eaves CJ. A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability. Nat Med 2008; 14:1384-9; PMID:19029987; http://dx.doi.org/10.1038/nm.1791
  • Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, Asselin-Labat ML, Gyorki DE, Ward T, Partanen A, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 2009; 15:907-13; PMID:19648928; http://dx.doi.org/10.1038/nm.2000
  • Keller PJ, Lin AF, Arendt LM, Klebba I, Jones AD, Rudnick JA, DiMeo TA, Gilmore H, Jefferson DM, Graham RA, et al. Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines. Breast Cancer Res 2010; 12:R87; PMID:20964822; http://dx.doi.org/10.1186/bcr2755
  • Raouf A, Zhao Y, To K, Stingl J, Delaney A, Barbara M, Iscove N, Jones S, McKinney S, Emerman J, et al. Transcriptome analysis of the normal human mammary cell commitment and differentiation process. Cell Stem Cell 2008; 3:109-18; PMID:18593563; http://dx.doi.org/10.1016/j.stem.2008.05.018
  • Regan JL, Kendrick H, Magnay FA, Vafaizadeh V, Groner B, Smalley MJ. C-kit is required for growth and survival of the cells of origin of Brca1-mutation-associated breast cancer. Oncogene 2012; 31:869-83; PMID:21765473; http://dx.doi.org/10.1038/onc.2011.289
  • Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE. Generation of a functional mammary gland from a single stem cell. Nature 2006; 439:84-8; PMID:16397499; http://dx.doi.org/10.1038/nature04372
  • Stingl J, Eaves CJ, Zandieh I, Emerman JT. Characterization of bipotent mammary epithelial progenitor cells in normal adult human breast tissue. Breast Cancer Res Treat 2001; 67:93-109; PMID:11519870
  • Rios AC, Fu NY, Lindeman GJ, Visvader JE. In situ identification of bipotent stem cells in the mammary gland. Nature 2014; 506:322-7; PMID:24463516; http://dx.doi.org/10.1038/nature12948
  • Proia TA, Keller PJ, Gupta PB, Klebba I, Jones AD, Sedic M, Gilmore H, Tung N, Naber SP, Schnitt S, et al. Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate. Cell Stem Cell 2011; 8:149-63; PMID:21295272; http://dx.doi.org/10.1016/j.stem.2010.12.007
  • Phillips S, Prat A, Sedic M, Proia T, Wronski A, Mazumdar S, Skibinski A, Shirley SH, Perou CM, Gill G, et al. Cell-state transitions regulated by SLUG are critical for tissue regeneration and tumor initiation. Stem Cell Reports 2014; In Press
  • Guo W, Keckesova Z, Donaher JL, Shibue T, Tischler V, Reinhardt F, Itzkovitz S, Noske A, Zurrer-Hardi U, Bell G, et al. Slug and Sox9 cooperatively determine the mammary stem cell state. Cell 2012; 148:1015-28; PMID:22385965; http://dx.doi.org/10.1016/j.cell.2012.02.008
  • Nassour M, Idoux-Gillet Y, Selmi A, Come C, Faraldo ML, Deugnier MA, Savagner P. Slug controls stem/progenitor cell growth dynamics during mammary gland morphogenesis. PLoS One 2012; 7:e53498; PMID:23300933; http://dx.doi.org/10.1371/journal.pone.0053498
  • Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ. Purification and unique properties of mammary epithelial stem cells. Nature 2006; 439:993-7; PMID:16395311; http://dx.doi.org/10.1038/nature04496
  • Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003; 100:3983-8; PMID:12629218; http://dx.doi.org/10.1073/pnas.0530291100
  • Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133:704-15; PMID:18485877; http://dx.doi.org/10.1016/j.cell.2008.03.027
  • Bhat-Nakshatri P, Appaiah H, Ballas C, Pick-Franke P, Goulet R,Jr, Badve S, Srour EF, Nakshatri H. SLUG/SNAI2 and tumor necrosis factor generate breast cells with CD44+/CD24- phenotype. BMC Cancer 2010; 10:411,2407-10-411; PMID:20691079; http://dx.doi.org/10.1186/1471-2407-10-411
  • Morel AP, Lievre M, Thomas C, Hinkal G, Ansieau S, Puisieux A. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 2008; 3:e2888; PMID:18682804; http://dx.doi.org/10.1371/journal.pone.0002888
  • van Amerongen R, Bowman AN, Nusse R. Developmental stage and time dictate the fate of wnt/beta-catenin-responsive stem cells in the mammary gland. Cell Stem Cell 2012; 11:387-400; PMID:22863533; http://dx.doi.org/10.1016/j.stem.2012.05.023
  • Holm K, Hegardt C, Staaf J, Vallon-Christersson J, Jonsson G, Olsson H, Borg A, Ringner M. Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns. Breast Cancer Res 2010; 12:R36; PMID:20565864; http://dx.doi.org/10.1186/bcr2590 [doi]
  • Kagara N, Huynh KT, Kuo C, Okano H, Sim MS, Elashoff D, Chong K, Giuliano AE, Hoon DS. Epigenetic regulation of cancer stem cell genes in triple-negative breast cancer. Am J Pathol 2012; 181:257-67; PMID:22626806; http://dx.doi.org/10.1016/j.ajpath.2012.03.019 [doi]
  • Chang CJ, Yang JY, Xia W, Chen CT, Xie X, Chao CH, Woodward WA, Hsu JM, Hortobagyi GN, Hung MC. EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-beta-catenin signaling. Cancer Cell 2011; 19:86-100; PMID:21215703; http://dx.doi.org/10.1016/j.ccr.2010.10.035 [doi]
  • Yamamoto M, Ito T, Shimizu T, Ishida T, Semba K, Watanabe S, Yamaguchi N, Inoue J. Epigenetic alteration of the NF-kappaB-inducing kinase (NIK) gene is involved in enhanced NIK expression in basal-like breast cancer. Cancer Sci 2010; 101:2391-7; PMID:20735436; http://dx.doi.org/10.1111/j.1349-7006.2010.01685.x [doi]
  • Byler S, Goldgar S, Heerboth S, Leary M, Housman G, Moulton K, Sarkar S. Genetic and epigenetic aspects of breast cancer progression and therapy. Anticancer Res 2014; 34:1071-7; PMID:24596345; http://dx.doi.org/ 34/3/1071 [pii]
  • Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Goktuna SI, Ziegler PK, Canli O, Heijmans J, Huels DJ, Moreaux G, et al. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell 2013; 152:25-38; PMID:23273993; http://dx.doi.org/10.1016/j.cell.2012.12.012
  • Youssef KK, Lapouge G, Bouvree K, Rorive S, Brohee S, Appelstein O, Larsimont JC, Sukumaran V, Van de Sande B, Pucci D, et al. Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation. Nat Cell Biol 2012; 14:1282-94; PMID:23178882; http://dx.doi.org/10.1038/ncb2628
  • Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia De Herreros A. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2000; 2:84-9; PMID:10655587; http://dx.doi.org/10.1038/35000034
  • Sarrio D, Rodriguez-Pinilla SM, Hardisson D, Cano A, Moreno-Bueno G, Palacios J. Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res 2008; 68:989-97; PMID:18281472; http://dx.doi.org/10.1158/0008-5472.CAN-07-2017 [doi]
  • de Herreros AG, Peiro S, Nassour M, Savagner P. Snail family regulation and epithelial mesenchymal transitions in breast cancer progression. J Mammary Gland Biol Neoplasia 2010; 15:135-47; PMID:20455012; http://dx.doi.org/10.1007/s10911-010-9179-8
  • Liu T, Zhang X, Shang M, Zhang Y, Xia B, Niu M, Liu Y, Pang D. Dysregulated expression of slug, vimentin, and E-cadherin correlates with poor clinical outcome in patients with basal-like breast cancer. J Surg Oncol 2013; 107:188-94; PMID:22886823; http://dx.doi.org/10.1002/jso.23240
  • Alves CC, Carneiro F, Hoefler H, Becker KF. Role of the epithelial-mesenchymal transition regulator slug in primary human cancers. Front Biosci (Landmark Ed) 2009; 14:3035-50; PMID:19273255
  • Shook D, Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev 2003; 120:1351-83; PMID:14623443
  • Storci G, Sansone P, Trere D, Tavolari S, Taffurelli M, Ceccarelli C, Guarnieri T, Paterini P, Pariali M, Montanaro L, et al. The basal-like breast carcinoma phenotype is regulated by SLUG gene expression. J Pathol 2008; 214:25-37; PMID:17973239; http://dx.doi.org/10.1002/path.2254
  • Hajra KM, Chen DY, Fearon ER. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res 2002; 62:1613-8; PMID:11912130
  • Martin TA, Goyal A, Watkins G, Jiang WG. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol 2005; 12:488-96; PMID:15864483; http://dx.doi.org/10.1245/ASO.2005.04.010
  • Choi Y, Lee HJ, Jang MH, Gwak JM, Lee KS, Kim EJ, Kim HJ, Lee HE, Park SY. Epithelial-mesenchymal transition increases during the progression of in situ to invasive basal-like breast cancer. Hum Pathol 2013; 44:2581-9; PMID:24055090; http://dx.doi.org/10.1016/j.humpath.2013.07.003 [doi]
  • Leroy P, Mostov KE. Slug is required for cell survival during partial epithelial-mesenchymal transition of HGF-induced tubulogenesis. Mol Biol Cell 2007; 18:1943-52; PMID:17344479; http://dx.doi.org/10.1091/mbc.E06-09-0823
  • Ewald AJ, Huebner RJ, Palsdottir H, Lee JK, Perez MJ, Jorgens DM, Tauscher AN, Cheung KJ, Werb Z, Auer M. Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium. J Cell Sci 2012; 125:2638-54; PMID:22344263; http://dx.doi.org/10.1242/jcs.096875
  • Sorlie T, Wang Y, Xiao C, Johnsen H, Naume B, Samaha RR, Borresen-Dale AL. Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: Gene expression analyses across three different platforms. BMC Genomics 2006; 7:127; PMID:16729877; http://dx.doi.org/ 1471-2164-7-127 [pii]
  • Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 2005; 11:5678-85; PMID:16115903; http://dx.doi.org/ 11/16/5678 [pii]
  • Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al. Molecular portraits of human breast tumours. Nature 2000; 406:747-52; PMID:10963602; http://dx.doi.org/10.1038/35021093
  • Rakha EA, Ellis IO. Triple-negative/basal-like breast cancer: Review. Pathology 2009; 41:40-7; PMID:19089739; http://dx.doi.org/10.1080/00313020802563510
  • Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001; 98:10869-74; PMID:11553815; http://dx.doi.org/10.1073/pnas.191367098
  • Bertucci F, Finetti P, Birnbaum D. Basal breast cancer: A complex and deadly molecular subtype. Curr Mol Med 2012; 12:96-110; PMID:22082486; http://dx.doi.org/ BSP/CMM/E-Pub/00017 [pii]
  • Ishihara A, Tsuda H, Kitagawa K, Yoneda M, Shiraishi T. Morphological characteristics of basal-like subtype of breast carcinoma with special reference to cytopathological features. Breast Cancer 2009; 16:179-85; PMID:19466513; http://dx.doi.org/10.1007/s12282-009-0108-x [doi]
  • Arnes JB, Brunet JS, Stefansson I, Begin LR, Wong N, Chappuis PO, Akslen LA, Foulkes WD. Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer. Clin Cancer Res 2005; 11:4003-11; PMID:15930334; http://dx.doi.org/ 11/11/4003 [pii]
  • Foulkes WD, Brunet JS, Stefansson IM, Straume O, Chappuis PO, Begin LR, Hamel N, Goffin JR, Wong N, Trudel M, et al. The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer. Cancer Res 2004; 64:830-5; PMID:14871808
  • Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT, Perou CM. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 2006; 19:264-71; PMID:16341146; http://dx.doi.org/ 3800528 [pii]
  • Gusterson B. Do ‘basal-like’ breast cancers really exist? Nat Rev Cancer 2009; 9:128-34; PMID:19132008; http://dx.doi.org/10.1038/nrc2571; 10.1038/nrc2571
  • Bertucci F, Cervera N, Birnbaum D. A gene signature in breast cancer. N Engl J Med 2007; 356:1887,8; author reply 1887-8; PMID:17476019; http://dx.doi.org/ 356/18/1887 [pii]
  • Charafe-Jauffret E, Ginestier C, Monville F, Finetti P, Adelaide J, Cervera N, Fekairi S, Xerri L, Jacquemier J, Birnbaum D, et al. Gene expression profiling of breast cell lines identifies potential new basal markers. Oncogene 2006; 25:2273-84; PMID:16288205; http://dx.doi.org/ 1209254 [pii]
  • Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med 2007; 356:217-26; PMID:17229949; http://dx.doi.org/ 356/3/217 [pii]
  • Zvelebil M, Oliemuller E, Gao Q, Wansbury O, Mackay A, Kendrick H, Smalley MJ, Reis-Filho JS, Howard BA. Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers. Breast Cancer Res 2013; 15:R25; PMID:23506684; http://dx.doi.org/10.1186/bcr3403
  • Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 2008; 10:R25; PMID:18366788; http://dx.doi.org/10.1186/bcr1982 [doi]
  • Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R, Jr, Badve S, Nakshatri H. CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: An early step necessary for metastasis. Breast Cancer Res 2006; 8:R59; PMID:17062128; http://dx.doi.org/ bcr1610 [pii]
  • Park SY, Lee HE, Li H, Shipitsin M, Gelman R, Polyak K. Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res 2010; 16:876-87; PMID:20103682; http://dx.doi.org/10.1158/1078-0432.CCR-09-1532 [doi]
  • Honeth G, Bendahl PO, Ringner M, Saal LH, Gruvberger-Saal SK, Lovgren K, Grabau D, Ferno M, Borg A, Hegardt C. The CD44+/CD24- phenotype is enriched in basal-like breast tumors. Breast Cancer Res 2008; 10:R53; PMID:18559090; http://dx.doi.org/10.1186/bcr2108
  • Keller PJ, Arendt LM, Kuperwasser C. Stem cell maintenance of the mammary gland: It takes two. Cell Stem Cell 2011; 9:496-7; PMID:22136921; http://dx.doi.org/10.1016/j.stem.2011.11.008
  • Keller PJ, Arendt LM, Skibinski A, Logvinenko T, Klebba I, Dong S, Smith AE, Prat A, Perou CM, Gilmore H, et al. Defining the cellular precursors to human breast cancer. Proc Natl Acad Sci U S A 2012; 109:2772-7; PMID:21940501; http://dx.doi.org/10.1073/pnas.1017626108
  • Molyneux G, Geyer FC, Magnay FA, McCarthy A, Kendrick H, Natrajan R, Mackay A, Grigoriadis A, Tutt A, Ashworth A, et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell 2010; 7:403-17; PMID:20804975; http://dx.doi.org/10.1016/j.stem.2010.07.010
  • Furuta S, Jiang X, Gu B, Cheng E, Chen PL, Lee WH. Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary epithelial cells. Proc Natl Acad Sci U S A 2005; 102:9176-81; PMID:15967981; http://dx.doi.org/ 0503793102 [pii]
  • Kubista M, Rosner M, Kubista E, Bernaschek G, Hengstschlager M. Brca1 regulates in vitro differentiation of mammary epithelial cells. Oncogene 2002; 21:4747-56; PMID:12101413; http://dx.doi.org/10.1038/sj.onc.1205580 [doi]
  • Liu S, Ginestier C, Charafe-Jauffret E, Foco H, Kleer CG, Merajver SD, Dontu G, Wicha MS. BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci U S A 2008; 105:1680-5; PMID:18230721; http://dx.doi.org/10.1073/pnas.0711613105 [doi]
  • Cloos PA, Christensen J, Agger K, Helin K. Erasing the methyl mark: Histone demethylases at the center of cellular differentiation and disease. Genes Dev 2008; 22:1115-40; PMID:18451103; http://dx.doi.org/10.1101/gad.1652908
  • Peinado H, Ballestar E, Esteller M, Cano A. Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol Cell Biol 2004; 24:306-19; PMID:14673164
  • Hou Z, Peng H, Ayyanathan K, Yan KP, Langer EM, Longmore GD, Rauscher FJ, 3rd. The LIM protein AJUBA recruits protein arginine methyltransferase 5 to mediate SNAIL-dependent transcriptional repression. Mol Cell Biol 2008; 28:3198-207; PMID:18347060; http://dx.doi.org/10.1128/MCB.01435-07
  • Dong C, Wu Y, Wang Y, Wang C, Kang T, Rychahou PG, Chi YI, Evers BM, Zhou BP. Interaction with Suv39H1 is critical for snail-mediated E-cadherin repression in breast cancer. Oncogene 2013; 32:1351-62; PMID:22562246; http://dx.doi.org/10.1038/onc.2012.169 [doi]
  • Dong C, Wu Y, Yao J, Wang Y, Yu Y, Rychahou PG, Evers BM, Zhou BP. G9a interacts with snail and is critical for snail-mediated E-cadherin repression in human breast cancer. J Clin Invest 2012; 122:1469-86; PMID:22406531; http://dx.doi.org/10.1172/JCI57349 [doi]
  • Herranz N, Pasini D, Diaz VM, Franci C, Gutierrez A, Dave N, Escriva M, Hernandez-Munoz I, Di Croce L, Helin K, et al. Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor. Mol Cell Biol 2008; 28:4772-81; PMID:18519590; http://dx.doi.org/10.1128/MCB.00323-08
  • Lin T, Ponn A, Hu X, Law BK, Lu J. Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition. Oncogene 2010; 29:4896-904; PMID:20562920; http://dx.doi.org/10.1038/onc.2010.234
  • Shi YJ, Matson C, Lan F, Iwase S, Baba T, Shi Y. Regulation of LSD1 histone demethylase activity by its associated factors. Mol Cell 2005; 19:857-64; PMID:16140033; http://dx.doi.org/10.1016/j.molcel.2005.08.027
  • Saleque S, Kim J, Rooke HM, Orkin SH. Epigenetic regulation of hematopoietic differentiation by gfi-1 and gfi-1b is mediated by the cofactors CoREST and LSD1. Mol Cell 2007; 27:562-72; PMID:17707228; http://dx.doi.org/10.1016/j.molcel.2007.06.039
  • Lin Y, Wu Y, Li J, Dong C, Ye X, Chi YI, Evers BM, Zhou BP. The SNAG domain of Snail1 functions as a molecular hook for recruiting lysine-specific demethylase 1. EMBO J 2010; 29:1803-16; PMID:20389281; http://dx.doi.org/10.1038/emboj.2010.63 [doi]
  • Wu ZQ, Li XY, Hu CY, Ford M, Kleer CG, Weiss SJ. Canonical wnt signaling regulates slug activity and links epithelial-mesenchymal transition with epigenetic breast cancer 1, early onset (BRCA1) repression. Proc Natl Acad Sci U S A 2012; 109:16654-9; PMID:23011797; http://dx.doi.org/10.1073/pnas.1205822109
  • Lim S, Janzer A, Becker A, Zimmer A, Schule R, Buettner R, Kirfel J. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis 2010; 31:512-20; PMID:20042638; http://dx.doi.org/10.1093/carcin/bgp324.

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