Home LiteratureArticle Details
PMID: 23344542 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Regulatory networks defining EMT during cancer initiation and progression.

Nature reviews. Cancer ·Vol. 13 ·No. 2 ·2013-02-00 ·Pages 97-110

De Craene B, Berx G

Abstract

Epithelial to mesenchymal transition (EMT) is essential for driving plasticity during development, but is an unintentional behaviour of cells during cancer progression. The EMT-associated reprogramming of cells not only suggests that fundamental changes may occur to several regulatory networks but also that an intimate interplay exists between them. Disturbance of a controlled epithelial balance is triggered by altering several layers of regulation, including the transcriptional and translational machinery, expression of non-coding RNAs, alternative splicing and protein stability.

MeSH Terms
Animals Disease Progression Epithelial Cells/metabolism,pathology Epithelial-Mesenchymal Transition Humans Neoplasms/genetics,metabolism,pathology
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
De Craene Bram
Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Zwijnaarde, Belgium.
Berx Geert
References (202)
202 references, click to expand
  1. MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma.
    Oncogene. 2013 Jan 17;32(3):277-85 PMID: 22391564
  2. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells.
    EMBO Rep. 2008 Jun;9(6):582-9 PMID: 18483486
  3. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization.
    Nat Med. 2011 Aug 07;17(9):1101-8 PMID: 21822286
  4. A p120 catenin isoform switch affects Rho activity, induces tumor cell invasion, and predicts metastatic disease.
    J Biol Chem. 2008 Jun 27;283(26):18344-54 PMID: 18407999
  5. The LZT proteins; the LIV-1 subfamily of zinc transporters.
    Biochim Biophys Acta. 2003 Apr 1;1611(1-2):16-30 PMID: 12659941
  6. Deletion of the SLUG (SNAI2) gene results in human piebaldism.
    Am J Med Genet A. 2003 Oct 1;122A(2):125-32 PMID: 12955764
  7. Lysyl oxidase: from basic science to future cancer treatment.
    Cell Struct Funct. 2012;37(1):75-80 PMID: 22453058
  8. A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts.
    Cell Stem Cell. 2010 Jul 2;7(1):51-63 PMID: 20621050
  9. DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells.
    Oncogene. 2005 Mar 31;24(14):2375-85 PMID: 15674322
  10. Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1.
    Cancer Cell. 2012 Dec 11;22(6):709-24 PMID: 23201163
  11. Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-regulation in intestinal gastric cancer.
    J Pathol. 2012 Sep;228(1):31-44 PMID: 22450781
  12. Brachyury expression predicts poor prognosis at early stages of colorectal cancer.
    Eur J Cancer. 2011 May;47(7):1080-5 PMID: 21220197
  13. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers.
    Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10069-74 PMID: 17537911
  14. The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation.
    J Biol Chem. 2010 Feb 5;285(6):3794-3805 PMID: 19955572
  15. The epithelial-mesenchymal transition generates cells with properties of stem cells.
    Cell. 2008 May 16;133(4):704-15 PMID: 18485877
  16. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells.
    Nat Cell Biol. 2000 Feb;2(2):84-9 PMID: 10655587
  17. To differentiate or not--routes towards metastasis.
    Nat Rev Cancer. 2012 May 11;12(6):425-36 PMID: 22576165
  18. Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition.
    Oncogene. 2010 Sep 2;29(35):4896-904 PMID: 20562920
  19. Brachyury, a driver of the epithelial-mesenchymal transition, is overexpressed in human lung tumors: an opportunity for novel interventions against lung cancer.
    Clin Cancer Res. 2012 Jul 15;18(14):3868-79 PMID: 22611028
  20. Activation of the ATM-Snail pathway promotes breast cancer metastasis.
    J Mol Cell Biol. 2012 Oct;4(5):304-15 PMID: 22923499
  21. Methylation patterns of the E-cadherin 5' CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression.
    J Biol Chem. 2000 Jan 28;275(4):2727-32 PMID: 10644736
  22. SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions.
    Nucleic Acids Res. 2005 Nov 24;33(20):6566-78 PMID: 16314317
  23. Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis.
    Cancer Res. 2011 Jan 1;71(1):245-54 PMID: 21199805
  24. ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1.
    Oncogene. 2010 Jun 17;29(24):3490-500 PMID: 20418909
  25. The epithelial-mesenchymal transition under control: global programs to regulate epithelial plasticity.
    Semin Cancer Biol. 2012 Oct;22(5-6):361-8 PMID: 22613485
  26. H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM.
    Cancer Res. 2010 Oct 15;70(20):7830-40 PMID: 20940408
  27. Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2.
    Nat Cell Biol. 2012 Nov;14(11):1212-22 PMID: 23086238
  28. Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation.
    EMBO J. 2012 Jan 4;31(1):29-43 PMID: 21952048
  29. TGF-beta-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI.
    Nat Cell Biol. 2010 Mar;12(3):286-93 PMID: 20154680
  30. Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin.
    J Pathol. 2007 Apr;211(5):507-515 PMID: 17299729
  31. Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas.
    Virchows Arch. 2011 Mar;458(3):313-22 PMID: 21225432
  32. Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.
    Mol Cell Biol. 2004 Jan;24(1):306-19 PMID: 14673164
  33. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition.
    Genes Dev. 2008 Mar 15;22(6):756-69 PMID: 18347095
  34. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion.
    Mol Cell. 2001 Jun;7(6):1267-78 PMID: 11430829
  35. EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
    PLoS Genet. 2012;8(5):e1002723 PMID: 22654675
  36. Defining the E-cadherin repressor interactome in epithelial-mesenchymal transition: the PMC42 model as a case study.
    Cells Tissues Organs. 2011;193(1-2):23-40 PMID: 21051859
  37. Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis.
    Oncogene. 2012 Apr 19;31(16):2062-74 PMID: 21874049
  38. Snail blocks the cell cycle and confers resistance to cell death.
    Genes Dev. 2004 May 15;18(10):1131-43 PMID: 15155580
  39. Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming.
    Cell Stem Cell. 2010 Jul 2;7(1):64-77 PMID: 20621051
  40. Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype.
    Cancer Res. 2008 Feb 15;68(4):989-97 PMID: 18281472
  41. TGF-β drives epithelial-mesenchymal transition through δEF1-mediated downregulation of ESRP.
    Oncogene. 2012 Jun 28;31(26):3190-201 PMID: 22037216
  42. Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer.
    Mol Carcinog. 2011 Dec;50(12):931-44 PMID: 21400613
  43. In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma.
    Cell. 2011 Oct 14;147(2):382-95 PMID: 22000016
  44. Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion.
    Cancer Cell. 2009 May 5;15(5):416-28 PMID: 19411070
  45. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells.
    Cell. 2011 Nov 11;147(4):759-72 PMID: 22078877
  46. Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates transcriptional repression of E-cadherin.
    J Biol Chem. 2005 Oct 21;280(42):35477-89 PMID: 16061479
  47. Key signalling nodes in mammary gland development and cancer. The Snail1-Twist1 conspiracy in malignant breast cancer progression.
    Breast Cancer Res. 2010;12(3):206 PMID: 20594364
  48. Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor.
    Mol Cell Biol. 2008 Aug;28(15):4772-81 PMID: 18519590
  49. Wnt signaling regulates Snai1 expression and cellular localization in the mouse intestinal epithelial stem cell niche.
    Stem Cells Dev. 2011 Apr;20(4):737-45 PMID: 20670162
  50. Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence.
    Cancer Res. 2006 Dec 1;66(23):11341-7 PMID: 17145880
  51. Lysyl oxidase-like 2 deaminates lysine 4 in histone H3.
    Mol Cell. 2012 May 11;46(3):369-76 PMID: 22483618
  52. E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines.
    Br J Cancer. 2006 Mar 13;94(5):661-71 PMID: 16495925
  53. Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene.
    Oncogene. 2001 Jun 28;20(29):3814-23 PMID: 11439345
  54. Expression and significance of Six1 and Ezrin in cervical cancer tissue.
    Tumour Biol. 2011 Dec;32(6):1241-7 PMID: 21874375
  55. 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 Oct 1;66(19):9543-56 PMID: 17018611
  56. Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer.
    Cell Stem Cell. 2010 Sep 3;7(3):299-313 PMID: 20804967
  57. Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells.
    BMC Genomics. 2010 Nov 25;11:669 PMID: 21108828
  58. Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels.
    Cancer Res. 2010 Jul 1;70(13):5226-37 PMID: 20551052
  59. A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression.
    EMBO J. 2005 Oct 5;24(19):3446-58 PMID: 16096638
  60. Involvement of members of the cadherin superfamily in cancer.
    Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a003129 PMID: 20457567
  61. Down-regulation of microRNAs of the miR-200 family and miR-205, and an altered expression of classic and desmosomal cadherins in spindle cell carcinoma of the head and neck--hallmark of epithelial-mesenchymal transition.
    Hum Pathol. 2011 Apr;42(4):482-8 PMID: 21237487
  62. miR-34 miRNAs provide a barrier for somatic cell reprogramming.
    Nat Cell Biol. 2011 Oct 23;13(11):1353-60 PMID: 22020437
  63. Role of CK1 in GSK3beta-mediated phosphorylation and degradation of snail.
    Oncogene. 2010 May 27;29(21):3124-33 PMID: 20305697
  64. The expression of the miRNA-200 family in endometrial endometrioid carcinoma.
    Gynecol Oncol. 2011 Jan;120(1):56-62 PMID: 21035172
  65. Analysis of the E-cadherin repressor Snail in primary human cancers.
    Cells Tissues Organs. 2007;185(1-3):204-12 PMID: 17587826
  66. Lysine-specific demethylase 1 (LSD1/KDM1A/AOF2/BHC110) is expressed and is an epigenetic drug target in chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma.
    Hum Pathol. 2012 Aug;43(8):1300-7 PMID: 22245111
  67. The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition.
    J Cell Biol. 1997 Jun 16;137(6):1403-19 PMID: 9182671
  68. microRNA-92a promotes lymph node metastasis of human esophageal squamous cell carcinoma via E-cadherin.
    J Biol Chem. 2011 Mar 25;286(12):10725-34 PMID: 21148309
  69. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability.
    Nature. 2005 Jul 7;436(7047):123-7 PMID: 16001073
  70. The rationale for targeting the LOX family in cancer.
    Nat Rev Cancer. 2012 Jul 19;12(8):540-52 PMID: 22810810
  71. A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer.
    Gynecol Oncol. 2009 Sep;114(3):457-64 PMID: 19501389
  72. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors.
    Cancer Res. 2007 Mar 15;67(6):2649-56 PMID: 17363585
  73. Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition.
    Nat Cell Biol. 2010 Oct;12(10):982-92 PMID: 20818389
  74. Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition.
    J Cell Biol. 2005 Jan 3;168(1):29-33 PMID: 15631989
  75. Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition.
    EMBO J. 2010 Nov 17;29(22):3787-96 PMID: 20959806
  76. p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2.
    J Exp Med. 2011 May 9;208(5):875-83 PMID: 21518799
  77. Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene.
    J Cell Biol. 2010 Oct 4;191(1):87-99 PMID: 20876280
  78. Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers.
    Front Biosci (Landmark Ed). 2009 Jan 01;14:3035-50 PMID: 19273255
  79. p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs.
    Nat Cell Biol. 2011 Mar;13(3):317-23 PMID: 21336307
  80. Gene expression of mesenchyme forkhead 1 (FOXC2) significantly correlates with the degree of lymph node metastasis in colorectal cancer.
    Int Surg. 2011 Jul-Sep;96(3):207-16 PMID: 22216698
  81. The transcription factor snail induces tumor cell invasion through modulation of the epithelial cell differentiation program.
    Cancer Res. 2005 Jul 15;65(14):6237-44 PMID: 16024625
  82. The ins and outs of the epithelial to mesenchymal transition in health and disease.
    Annu Rev Cell Dev Biol. 2011;27:347-76 PMID: 21740232
  83. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells.
    Cell. 2009 Aug 7;138(3):592-603 PMID: 19665978
  84. Cancer development induced by graded expression of Snail in mice.
    Hum Mol Genet. 2005 Nov 15;14(22):3449-61 PMID: 16207734
  85. Regulation of SNAIL1 and E-cadherin function by DNMT1 in a DNA methylation-independent context.
    Nucleic Acids Res. 2011 Nov;39(21):9194-205 PMID: 21846773
  86. Transcription factor 8 activates R-Ras to regulate angiogenesis.
    Biochem Biophys Res Commun. 2009 Feb 6;379(2):510-3 PMID: 19116136
  87. Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene.
    Mol Cell. 2005 Dec 22;20(6):881-90 PMID: 16364913
  88. ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing.
    Mol Cell. 2009 Mar 13;33(5):591-601 PMID: 19285943
  89. LOXL2 in epithelial cell plasticity and tumor progression.
    Future Oncol. 2012 Sep;8(9):1095-108 PMID: 23030485
  90. The F-box protein Ppa is a common regulator of core EMT factors Twist, Snail, Slug, and Sip1.
    J Cell Biol. 2011 Jul 11;194(1):17-25 PMID: 21727196
  91. Increased expression of bHLH transcription factor E2A (TCF3) in prostate cancer promotes proliferation and confers resistance to doxorubicin induced apoptosis.
    Biochem Biophys Res Commun. 2012 May 25;422(1):146-51 PMID: 22564737
  92. Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells.
    Mol Cell. 2010 Sep 10;39(5):761-72 PMID: 20832727
  93. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.
    Genes Dev. 2008 Apr 1;22(7):894-907 PMID: 18381893
  94. A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions.
    J Biol Chem. 2001 Jul 20;276(29):27424-31 PMID: 11309385
  95. 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 Oct 9;109(41):16654-9 PMID: 23011797
  96. Prognostic role of Twist, Slug, and Foxc2 expression in stage I non-small-cell lung cancer after curative resection.
    Clin Lung Cancer. 2012 Jul;13(4):280-7 PMID: 22178381
  97. G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer.
    J Clin Invest. 2012 Apr;122(4):1469-86 PMID: 22406531
  98. Cancer epigenetics reaches mainstream oncology.
    Nat Med. 2011 Mar;17(3):330-9 PMID: 21386836
  99. Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer.
    PLoS One. 2012;7(4):e35065 PMID: 22493729
  100. N-WASP-mediated invadopodium formation is involved in intravasation and lung metastasis of mammary tumors.
    J Cell Sci. 2012 Feb 1;125(Pt 3):724-34 PMID: 22389406
  101. The Spemann organizer gene, Goosecoid, promotes tumor metastasis.
    Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):18969-74 PMID: 17142318
  102. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs.
    Nat Cell Biol. 2009 Dec;11(12):1487-95 PMID: 19935649
  103. Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition.
    J Clin Invest. 2009 Sep;119(9):2663-77 PMID: 19726883
  104. Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer.
    J Transl Med. 2012 Sep 06;10:186 PMID: 22954417
  105. Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition.
    Cancer Cell. 2009 May 5;15(5):402-15 PMID: 19411069
  106. Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition.
    Nat Struct Mol Biol. 2011 Jul 03;18(8):867-74 PMID: 21725293
  107. Exon-level microarray analyses identify alternative splicing programs in breast cancer.
    Mol Cancer Res. 2010 Jul;8(7):961-74 PMID: 20605923
  108. Mutant p53 gain-of-function induces epithelial-mesenchymal transition through modulation of the miR-130b-ZEB1 axis.
    Oncogene. 2013 Jul 4;32(27):3286-95 PMID: 22847613
  109. Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells.
    PLoS One. 2010 Aug 27;5(8):e12445 PMID: 20805998
  110. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression.
    Nat Cell Biol. 2000 Feb;2(2):76-83 PMID: 10655586
  111. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology.
    Carcinogenesis. 2010 Mar;31(3):512-20 PMID: 20042638
  112. MicroRNA control of epithelial-mesenchymal transition and metastasis.
    Cancer Metastasis Rev. 2012 Dec;31(3-4):653-62 PMID: 22684369
  113. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness.
    Cell Mol Life Sci. 2012 Oct;69(20):3429-56 PMID: 22945800
  114. The miRNA-200 family and miRNA-9 exhibit differential expression in primary versus corresponding metastatic tissue in breast cancer.
    Breast Cancer Res Treat. 2012 Jul;134(1):207-17 PMID: 22294488
  115. A putative role for microRNA-205 in mammary epithelial cell progenitors.
    J Cell Sci. 2010 Feb 15;123(Pt 4):606-18 PMID: 20103531
  116. TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition.
    Oncogene. 2008 Apr 17;27(18):2635-47 PMID: 17968309
  117. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis.
    Nat Cell Biol. 2010 Mar;12(3):247-56 PMID: 20173740
  118. Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma.
    Am J Pathol. 2009 Mar;174(3):736-45 PMID: 19179615
  119. Epithelial-mesenchymal transitions in tumour progression.
    Nat Rev Cancer. 2002 Jun;2(6):442-54 PMID: 12189386
  120. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity.
    Cancer Res. 2009 Feb 1;69(3):1135-42 PMID: 19155302
  121. Krüppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion.
    Cancer Res. 2007 Aug 1;67(15):7184-93 PMID: 17671186
  122. MiR-101 and Mcl-1 in non-small-cell lung cancer: expression profile and clinical significance.
    Med Oncol. 2012 Sep;29(3):1681-6 PMID: 21993632
  123. p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug.
    Nat Cell Biol. 2009 Jun;11(6):694-704 PMID: 19448627
  124. Wnt-dependent regulation of the E-cadherin repressor snail.
    J Biol Chem. 2005 Mar 25;280(12):11740-8 PMID: 15647282
  125. Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer.
    Int J Cancer. 2011 Mar 15;128(6):1327-34 PMID: 20473948
  126. Association of the SUV39H1 histone methyltransferase with the DNA methyltransferase 1 at mRNA expression level in primary colorectal cancer.
    Int J Cancer. 2007 Nov 15;121(10):2192-7 PMID: 17657744
  127. Epithelial-mesenchymal transitions in development and disease.
    Cell. 2009 Nov 25;139(5):871-90 PMID: 19945376
  128. Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression.
    Nat Rev Cancer. 2005 Sep;5(9):744-9 PMID: 16148886
  129. The EMT regulator Zeb2/Sip1 is essential for murine embryonic hematopoietic stem/progenitor cell differentiation and mobilization.
    Blood. 2011 May 26;117(21):5620-30 PMID: 21355089
  130. Suppression of the epithelial-mesenchymal transition by Grainyhead-like-2.
    Cancer Res. 2012 May 1;72(9):2440-53 PMID: 22379025
  131. The emerging role of p53 in stem cells.
    Trends Mol Med. 2012 Jan;18(1):6-12 PMID: 21907001
  132. Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions.
    Cancer Res. 2005 Apr 15;65(8):3179-84 PMID: 15833848
  133. FOXC2 is a novel prognostic factor in human esophageal squamous cell carcinoma.
    Ann Surg Oncol. 2011 Feb;18(2):535-42 PMID: 20803080
  134. Histone deacetylases and cancer.
    Mol Oncol. 2012 Dec;6(6):579-89 PMID: 22963873
  135. The epithelial cell default-phenotype hypothesis and its implications for cancer.
    Bioessays. 1997 Aug;19(8):705-9 PMID: 9264253
  136. Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR.
    Clin Chem. 2008 Oct;54(10):1696-704 PMID: 18719201
  137. A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition.
    J Cell Biol. 2011 Oct 31;195(3):417-33 PMID: 22024162
  138. MIR-99a and MIR-99b modulate TGF-β induced epithelial to mesenchymal plasticity in normal murine mammary gland cells.
    PLoS One. 2012;7(1):e31032 PMID: 22299047
  139. Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics.
    Cancer Res. 2009 May 15;69(10):4116-24 PMID: 19435916
  140. An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype.
    PLoS Genet. 2011 Aug;7(8):e1002218 PMID: 21876675
  141. Direct evidence for epithelial-mesenchymal transitions in breast cancer.
    Cancer Res. 2008 Feb 1;68(3):937-45 PMID: 18245497
  142. The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells.
    J Clin Invest. 2010 Feb;120(2):533-44 PMID: 20071775
  143. Direct repression of cyclin D1 by SIP1 attenuates cell cycle progression in cells undergoing an epithelial mesenchymal transition.
    Mol Biol Cell. 2007 Nov;18(11):4615-24 PMID: 17855508
  144. Downregulation of miR-205 and miR-31 confers resistance to chemotherapy-induced apoptosis in prostate cancer cells.
    Cell Death Dis. 2010 Dec 09;1:e105 PMID: 21368878
  145. Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence.
    Cancer Cell. 2008 Jul 8;14(1):79-89 PMID: 18598946
  146. Independent repressor domains in ZEB regulate muscle and T-cell differentiation.
    Mol Cell Biol. 1999 Dec;19(12):7961-71 PMID: 10567522
  147. Snail represses the splicing regulator epithelial splicing regulatory protein 1 to promote epithelial-mesenchymal transition.
    J Biol Chem. 2012 Oct 19;287(43):36435-42 PMID: 22961986
  148. The critical role of the class III histone deacetylase SIRT1 in cancer.
    Cancer Res. 2009 Mar 1;69(5):1702-5 PMID: 19244112
  149. TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway.
    Mol Cell Biol. 2008 Apr;28(7):2426-36 PMID: 18227151
  150. MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion.
    Eur J Cancer. 2010 Aug;46(12):2295-303 PMID: 20712078
  151. Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney.
    EMBO J. 2006 Nov 29;25(23):5603-13 PMID: 17093497
  152. The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer.
    Cancer Res. 2008 Jan 15;68(2):537-44 PMID: 18199550
  153. EMT and dissemination precede pancreatic tumor formation.
    Cell. 2012 Jan 20;148(1-2):349-61 PMID: 22265420
  154. DNA hypermethylation of microRNA-34b/c has prognostic value for stage Ⅰ non-small cell lung cancer.
    Cancer Biol Ther. 2011 Mar 1;11(5):490-6 PMID: 21383543
  155. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.
    Nat Cell Biol. 2008 May;10(5):593-601 PMID: 18376396
  156. Slug, mammalian homologue gene of Drosophila escargot, promotes neuronal-differentiation through suppression of HEB/daughterless.
    Cell Cycle. 2010 Jul 15;9(14):2789-802 PMID: 20647756
  157. Signatures of microRNAs and selected microRNA target genes in human melanoma.
    Cancer Res. 2010 May 15;70(10):4163-73 PMID: 20442294
  158. Krüppel-like factor 8 emerges as an important regulator of cancer.
    Am J Transl Res. 2012;4(3):357-63 PMID: 22937212
  159. Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer.
    Nature. 2004 May 20;429(6989):298-302 PMID: 15129296
  160. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis.
    Cell. 2004 Jun 25;117(7):927-39 PMID: 15210113
  161. Interplay between HDAC3 and WDR5 is essential for hypoxia-induced epithelial-mesenchymal transition.
    Mol Cell. 2011 Sep 2;43(5):811-22 PMID: 21884981
  162. Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition.
    Nat Cell Biol. 2004 Oct;6(10):931-40 PMID: 15448698
  163. miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions.
    Cell Cycle. 2011 Dec 15;10(24):4256-71 PMID: 22134354
  164. In situ measurement of miR-205 in malignant melanoma tissue supports its role as a tumor suppressor microRNA.
    Lab Invest. 2012 Oct;92(10):1390-7 PMID: 22890556
  165. Downregulation of microRNA-200 in EBV-associated gastric carcinoma.
    Cancer Res. 2010 Jun 1;70(11):4719-27 PMID: 20484038
  166. Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells.
    PLoS One. 2010 Jan 13;5(1):e8697 PMID: 20084174
  167. Frequent downregulation of miR-34 family in human ovarian cancers.
    Clin Cancer Res. 2010 Feb 15;16(4):1119-28 PMID: 20145172
  168. MicroRNA-9: functional evolution of a conserved small regulatory RNA.
    RNA Biol. 2011 Jul-Aug;8(4):557-64 PMID: 21697652
  169. EMT and stem cell-like properties associated with miR-205 and miR-200 epigenetic silencing are early manifestations during carcinogen-induced transformation of human lung epithelial cells.
    Cancer Res. 2011 Apr 15;71(8):3087-97 PMID: 21363915
  170. Notch1 binds and induces degradation of Snail in hepatocellular carcinoma.
    BMC Biol. 2011 Nov 30;9:83 PMID: 22128911
  171. Targeting p21-activated kinase 1 (PAK1) to induce apoptosis of tumor cells.
    Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7177-82 PMID: 21482786
  172. Alternative splicing in fibroblast growth factor receptor 2 is associated with induced epithelial-mesenchymal transition in rat bladder carcinoma cells.
    Mol Biol Cell. 1994 Aug;5(8):851-62 PMID: 7803853
  173. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes.
    Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15449-54 PMID: 20713713
  174. The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway.
    Dev Cell. 2010 Dec 14;19(6):831-44 PMID: 21145499
  175. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2.
    J Biol Chem. 2008 May 30;283(22):14910-4 PMID: 18411277
  176. The SLUG zinc-finger protein represses E-cadherin in breast cancer.
    Cancer Res. 2002 Mar 15;62(6):1613-8 PMID: 11912130
  177. Identification of an mRNP complex regulating tumorigenesis at the translational elongation step.
    Mol Cell. 2011 Feb 18;41(4):419-31 PMID: 21329880
  178. Circulating tumour cells lacking cytokeratin in breast cancer: the importance of being mesenchymal.
    J Cell Mol Med. 2011 May;15(5):1066-70 PMID: 21352474
  179. Zinc-finger transcription factor Slug contributes to the function of the stem cell factor c-kit signaling pathway.
    Blood. 2002 Aug 15;100(4):1274-86 PMID: 12149208
  180. An emerging role for class I bHLH E2-2 proteins in EMT regulation and tumor progression.
    Cell Adh Migr. 2010 Jan-Mar;4(1):56-60 PMID: 20023376
  181. The class I bHLH factors E2-2A and E2-2B regulate EMT.
    J Cell Sci. 2009 Apr 1;122(Pt 7):1014-24 PMID: 19295128
  182. Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors.
    Br J Cancer. 2012 Jan 31;106(3):553-61 PMID: 22223089
  183. Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways.
    Breast Cancer Res. 2012 Jul 05;14(4):R100 PMID: 22765220
  184. A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis.
    Cell. 2009 Apr 3;137(1):87-98 PMID: 19345189
  185. SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis.
    Oncogene. 2012 Oct 25;31(43):4619-29 PMID: 22249256
  186. Specificity and prognostic validation of a polyclonal antibody to detect Six1 homeoprotein in ovarian cancer.
    Gynecol Oncol. 2012 May;125(2):451-7 PMID: 22333994
  187. Protein kinase D1 suppresses epithelial-to-mesenchymal transition through phosphorylation of snail.
    Cancer Res. 2010 Oct 15;70(20):7810-9 PMID: 20940406
  188. The microRNA-200 family is upregulated in endometrial carcinoma.
    PLoS One. 2011;6(8):e22828 PMID: 21897839
  189. Twist1-induced invadopodia formation promotes tumor metastasis.
    Cancer Cell. 2011 Mar 8;19(3):372-86 PMID: 21397860
  190. Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers.
    Int J Cancer. 2011 Feb 1;128(3):574-86 PMID: 20333681
  191. MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis.
    Gut. 2013 Sep;62(9):1315-26 PMID: 22735571
  192. Prognostic significance of miR-205 in endometrial cancer.
    PLoS One. 2012;7(4):e35158 PMID: 22514717
  193. Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.
    Genome Biol. 2007;8(5):R76 PMID: 17493263
  194. Snail1, Snail2, and E47 promote mammary epithelial branching morphogenesis.
    EMBO J. 2011 May 24;30(13):2662-74 PMID: 21610693
  195. Unraveling signalling cascades for the Snail family of transcription factors.
    Cell Signal. 2005 May;17(5):535-47 PMID: 15683729
  196. Modulation of several waves of gene expression during FGF-1 induced epithelial-mesenchymal transition of carcinoma cells.
    J Cell Biochem. 2008 Jun 1;104(3):826-39 PMID: 18189245
  197. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer.
    Science. 2008 Dec 12;322(5908):1695-9 PMID: 19008416
  198. An ESRP-regulated splicing programme is abrogated during the epithelial-mesenchymal transition.
    EMBO J. 2010 Oct 6;29(19):3286-300 PMID: 20711167
  199. Evolutionary functional analysis and molecular regulation of the ZEB transcription factors.
    Cell Mol Life Sci. 2012 Aug;69(15):2527-41 PMID: 22349261
  200. Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines.
    Oncogene. 2008 Aug 7;27(34):4690-701 PMID: 18408755
  201. P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis.
    Oncol Rep. 2012 May;27(5):1435-42 PMID: 22293972
  202. Interaction with Suv39H1 is critical for Snail-mediated E-cadherin repression in breast cancer.
    Oncogene. 2013 Mar 14;32(11):1351-62 PMID: 22562246
Article Info
Journal
Nature reviews. Cancer
Abbr.
Nat Rev Cancer
ISSN
1474-1768
DOI
10.1038/nrc3447
Published
2013-02-00
Pages
97-110
Language
English
Region
England
NLM ID
101124168
Subset
IM
Grants
Cancer Research UK · United Kingdom
External Links
PubMed source DOI: 10.1038/nrc3447 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2