A crossroad of microRNAs and immediate early genes (IEGs) encoding oncogenic transcription factors in breast cancer

Journal of Mammary Gland Biology and Neoplasia

Volumn 17, Issue 1, 2012, Pages 3-14

  Sas Chen, Aldema ^a   Avraham, Roi ^b   Yarden, Yosef ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

Growth factor; Immediate early gene; Metastasis; microRNA; Signal transduction

Indexed keywords

MICRORNA; TRANSCRIPTION FACTOR;

BREAST CANCER; BREAST CARCINOGENESIS; GENE ACTIVATION; GENE CONTROL; GENE EXPRESSION; GENETIC TRANSCRIPTION; HUMAN; IMMEDIATE EARLY GENE; ONCOGENE; REVIEW; SIGNAL TRANSDUCTION;

BREAST NEOPLASMS; FEMALE; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, IMMEDIATE-EARLY; HUMANS; MAMMARY GLANDS, HUMAN; MICRORNAS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 84858697998     PISSN: 10833021     EISSN: 15737039     Source Type: Journal    
DOI: 10.1007/s10911-012-9243-7     Document Type: Review

References (106)

1. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005;5(5):341-54. (Pubitemid 40637826)
2. Lanigan F, O'Connor D, Martin F, Gallagher WM. Molecular links between mammary gland development and breast cancer. Cell Mol Life Sci. 2007;64(24):3159-84.
3. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2(2):127-37. (Pubitemid 33674041)
4. Glauser DA, Schlegel W. Mechanisms of transcriptional regulation underlying temporal integration of signals. Nucleic Acids Res. 2006;34(18):5175-83. (Pubitemid 44742482)
5. Bieche I, Lerebours F, Tozlu S, Espie M, Marty M, Lidereau R. Molecular profiling of inflammatory breast cancer: identification of a poor-prognosis gene expression signature. Clin Cancer Res. 2004;10(20):6789-95. (Pubitemid 39383027)
6. Wilding G, Lippman ME, Gelmann EP. Effects of steroid hormones and peptide growth factors on protooncogene c-fos expression in human breast cancer cells. Cancer Res. 1988;48 (4):802-5. (Pubitemid 18061866)
7. Cochran BH, Reffel AC, Stiles CD. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell. 1983;33(3):939-47. (Pubitemid 13074000)
8. Lau LF, Nathans D. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci USA. 1987;84(5):1182-6. (Pubitemid 17027316)
9. Tullai JW, Schaffer ME, Mullenbrock S, Sholder G, Kasif S, Cooper GM. Immediate-early and delayed primary response genes are distinct in function and genomic architecture. J Biol Chem. 2007;282(33):23981-95. (Pubitemid 47328052)
10. Amit I, Citri A, Shay T, Lu Y, Katz M, Zhang F, et al. A module of negative feedback regulators defines growth factor signaling. Nat Genet. 2007;39(4):503-12. (Pubitemid 46514770)
11. Avril-Sassen S, Goldstein LD, Stingl J, Blenkiron C, Le Quesne J, Spiteri I, et al. Characterisation of microRNA expression in post-natal mouse mammary gland development. BMC Genomics. 2009;10548.
12. Tanaka T, Haneda S, Imakawa K, Sakai S, Nagaoka K. A micro- RNA, miR-101a, controls mammary gland development by regulating cyclooxygenase-2 expression. Differentiation. 2009;77 (2):181-7.
13. Wang L, Wang J. MicroRNA-mediated breast cancer metastasis: from primary site to distant organs. Oncogene. 2011.
14. Lee EB, Beug H, Hayman MJ. Mutational analysis of the role of the carboxy-terminal region of the v-erbB protein in erythroid cell transformation. Oncogene. 1993;8(5):1317-27. (Pubitemid 23129856)
15. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75(5):855-62. (Pubitemid 24014543)
16. Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian micro- RNAs predominantly act to decrease target mRNA levels. Nature. 2010;466(7308):835-40.
17. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature. 2008;455 (7209):64-71.
18. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N.Widespread changes in protein synthesis induced by microRNAs. Nature. 2008;455(7209):58-63.
19. Mukherji S, Ebert MS, Zheng GX, Tsang JS, Sharp PA, van Oudenaarden A. MicroRNAs can generate thresholds in target gene expression. Nat Genet. 2010;43(9):854-9.
20. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215-33.
21. Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen X, et al. A uniform system for microRNA annotation. Rna. 2003;9(3):277-9. (Pubitemid 36246165)
22. Hertel J, Lindemeyer M, Missal K, Fried C, Tanzer A, Flamm C, et al. The expansion of the metazoan microRNA repertoire. BMC Genomics. 2006;725.
23. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 2004;101(9):2999-3004. (Pubitemid 38327724)
24. Sevignani C, Calin GA, Nnadi SC, Shimizu M, Davuluri RV, Hyslop T, et al. MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc Natl Acad Sci USA. 2007;104(19):8017-22. (Pubitemid 47185868)
25. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065-70. (Pubitemid 41161233)
26. Lopez-Maury L, Marguerat S, Bahler J. Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation. Nat Rev Genet. 2008;9(8):583-93.
27. van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science. 2007;316(5824):575-9. (Pubitemid 46683138)
28. Gantier MP, McCoy CE, Rusinova I, Saulep D,Wang D, Xu D, et al. Analysis of microRNA turnover in mammalian cells following Dicer1 ablation. Nucleic Acids Res. 2010;39(13):5692-703.
29. Ramachandran V, Chen X. Degradation of microRNAs by a family of exoribonucleases in Arabidopsis. Science. 2008;321 (5895):1490-2.
30. Chatterjee S, Grosshans H. Active turnover modulates mature microRNA activity in Caenorhabditis elegans. Nature. 2009;461 (7263):546-9.
31. Burns DM, D'Ambrogio A, Nottrott S, Richter JD. CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation. Nature. 2010;473(7345):105-8.
32. Avraham R, Sas-Chen A, Manor O, Steinfeld I, Shalgi R, Tarcic G, et al. EGF decreases the abundance of microRNAs that restrain oncogenic transcription factors. Sci Signal. 2010;3(124): ra43.
33. Krol J, Busskamp V, Markiewicz I, Stadler MB, Ribi S, Richter J, et al. Characterizing light-regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAs. Cell. 2010;141(4):618-31.
34. Rajasethupathy P, Fiumara F, Sheridan R, Betel D, Puthanveettil SV, Russo JJ, et al. Characterization of small RNAs in Aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB. Neuron. 2009;63(6):803-17.
35. Rissland OS, Hong SJ, Bartel DP. MicroRNA destabilization enables dynamic regulation of the miR-16 family in response to cell-cycle changes. Mol Cell. 2010;43(6):993-1004.
36. Kim YK, Yeo J, Ha M, Kim B, Kim VN. Cell adhesiondependent control of microRNA decay. Mol Cell. 2011;43 (6):1005-14.
37. Buck AH, Perot J, Chisholm MA, Kumar DS, Tuddenham L, Cognat V, et al. Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection. Rna. 2010;16(2):307-15.
38. Cazalla D, Yario T, Steitz JA. Down-regulation of a host micro- RNA by a Herpesvirus saimiri noncoding RNA. Science. 2010;328(5985):1563-6.
39. Levine E, Zhang Z, Kuhlman T, Hwa T. Quantitative characteristics of gene regulation by small RNA. PLoS Biol. 2007;5(9): e229.
40. Mehta P, Goyal S, Wingreen NS. A quantitative comparison of sRNA-based and protein-based gene regulation. Mol Syst Biol. 2008;4221.
41. Alon U. Network motifs: theory and experimental approaches. Nat Rev Genet. 2007;8(6):450-61. (Pubitemid 46789247)
42. Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U. Network motifs: simple building blocks of complex networks. Science. 2002;298(5594):824-7. (Pubitemid 35231534)
43. Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction. Nat Rev Mol Cell Biol. 2010;11(4):252-63.
44. Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol. 2006;7(7):505-16. (Pubitemid 44036456)
45. Tsang J, Zhu J, van Oudenaarden A. MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Mol Cell. 2007;26(5):753-67. (Pubitemid 46856248)
46. Martinez HD, Jasavala RJ, Hinkson I, Fitzgerald LD, Trimmer JS, Kung HJ, et al. RNA editing of androgen receptor gene transcripts in prostate cancer cells. J Biol Chem. 2008;283 (44):29938-49.
47. Forman JJ, Legesse-Miller A, Coller HA. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci USA. 2008;105(39):14879-84.
48. Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelialmesenchymal transition. Cancer Res. 2008;68(19):7846-54.
49. Li X, Carthew RW. A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye. Cell. 2005;123(7):1267-77. (Pubitemid 41821784)
50. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15-20. (Pubitemid 40094598)
51. Kitano H. Biological robustness. Nat Rev Genet. 2004;5 (11):826-37. (Pubitemid 39457498)
52. Barker A, Giles KM, Epis MR, Zhang PM, Kalinowski F, Leedman PJ. Regulation of ErbB receptor signalling in cancer cells by micro- RNA. Curr Opin Pharmacol. 2010;10(6):655-61.
53. Hsu SD, Lin FM, Wu WY, Liang C, Huang WC, Chan WL, et al. miRTarBase: a database curates experimentally validated microRNAtarget interactions. Nucleic Acids Res. 2010;39(Database issue): D163-169.
54. Xiao F, Zuo Z, Cai G, Kang S, Gao X, Li T. miRecords: an integrated resource for microRNA-target interactions. Nucleic Acids Res. 2009;37(Database issue):D105-110.
55. Marshall CJ. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell. 1995;80(2):179-85.
56. Nakakuki T, Birtwistle MR, Saeki Y, Yumoto N, Ide K, Nagashima T, et al. Ligand-specific c-Fos expression emerges from the spatiotemporal control of ErbB network dynamics. Cell. 2010;141(5):884-96.
57. Greene SB, Gunaratne PH, Hammond SM, Rosen JM. A putative role for microRNA-205 in mammary epithelial cell progenitors. J Cell Sci. 2010;123(Pt 4):606-18.
58. Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G, et al. Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res. 2007;67(24):11612-20.
59. Mattie MD, Benz CC, Bowers J, Sensinger K,Wong L, Scott GK, et al. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer. 2006;524.
60. Greene SB, Herschkowitz JI, Rosen JM. Small players with big roles: microRNAs as targets to inhibit breast cancer progression. Curr Drug Targets. 2010;11(9):1059-73.
61. Iorio MV, Casalini P, Piovan C, Di Leva G, Merlo A, Triulzi T, et al. microRNA-205 regulates HER3 in human breast cancer. Cancer Res. 2009;69(6):2195-200.
62. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593-601. (Pubitemid 351627379)
63. Wu H, Zhu S, Mo YY. Suppression of cell growth and invasion by miR-205 in breast cancer. Cell Res. 2009;19(4):439-48.
64. Png KJ, Halberg N, Yoshida M, Tavazoie SF. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature. 2011;481(7380).
65. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451(7175):147-52.
66. McCafferty MP, McNeill RE, Miller N, Kerin MJ. Interactions between the estrogen receptor, its cofactors and microRNAs in breast cancer. Breast Cancer Res Treat. 2009;116(3):425-32.
67. Tessel MA, Krett NL, Rosen ST. Steroid receptor and microRNA regulation in cancer. Curr Opin Oncol. 2010;22(6):592-7.
68. Kondo N, Toyama T, Sugiura H, Fujii Y, Yamashita H. miR-206 Expression is down-regulated in estrogen receptor alpha-positive human breast cancer. Cancer Res. 2008;68(13):5004-8.
69. Zhao JJ, Lin J, Yang H, Kong W, He L, Ma X, et al. MicroRNA- 221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem. 2008;283(45):31079-86.
70. Pandey DP, Picard D. miR-22 inhibits estrogen signaling by directly targeting the estrogen receptor alpha mRNA. Mol Cell Biol. 2009;29(13):3783-90.
71. Di Leva G, Gasparini P, Piovan C, Ngankeu A, Garofalo M, Taccioli C, et al. MicroRNA cluster 221-222 and estrogen receptor alpha interactions in breast cancer. J Natl Cancer Inst. 2010;102(10):706-21.
72. Zhao Y, Deng C, Wang J, Xiao J, Gatalica Z, Recker RR, et al. Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer. Breast Cancer Res Treat. 2010;127(1):69-80.
73. Leivonen SK, Makela R, Ostling P, Kohonen P, Haapa-Paananen S, Kleivi K, et al. Protein lysate microarray analysis to identify microRNAs regulating estrogen receptor signaling in breast cancer cell lines. Oncogene. 2009;28(44):3926-36.
74. Christoffersen NR, Silahtaroglu A, Orom UA, Kauppinen S, Lund AH. miR-200b mediates post-transcriptional repression of ZFHX1B. Rna. 2007;13(8):1172-8. (Pubitemid 47080461)
75. Kato M, Zhang J, Wang M, Lanting L, Yuan H, Rossi JJ, et al. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci USA. 2007;104(9):3432-7. (Pubitemid 46364176)
76. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22 (7):894-907. (Pubitemid 351482843)
77. Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008;9(6):582-9. (Pubitemid 351772923)
78. Chen Y, Banda M, Speyer CL, Smith JS, Rabson AB, Gorski DH. Regulation of the expression and activity of the antiangiogenic homeobox gene GAX/MEOX2 by ZEB2 and microRNA-221. Mol Cell Biol. 2010;30(15):3902-13.
79. Saini S, Majid S, Yamamura S, Tabatabai L, Suh SO, Shahryari V, et al. Regulatory Role of mir-203 in Prostate Cancer Progression and Metastasis. Clin Cancer Res. 2010;17(16):5287-98.
80. Liu X, Wang C, Chen Z, Jin Y, Wang Y, Kolokythas A, et al. MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines. Biochem J. 2011;440(1):23-31.
81. Stinson S, Lackner MR, Adai AT, Yu N, Kim HJ, O'Brien C, et al. TRPS1 targeting by miR-221/222 promotes the epithelial-tomesenchymal transition in breast cancer. Sci Signal. 2010;4(177): ra41.
82. Schickel R, Park SM, Murmann AE, Peter ME. miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1. Mol Cell. 2010;38(6):908-15.
83. Hargreaves DC, Horng T, Medzhitov R. Control of inducible gene expression by signal-dependent transcriptional elongation. Cell. 2009;138(1):129-45.
84. Fraser P, Bickmore W. Nuclear organization of the genome and the potential for gene regulation. Nature. 2007;447(7143):413-7. (Pubitemid 46816747)
85. Chambeyron S, Bickmore WA. Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev. 2004;18(10):1119-30. (Pubitemid 38669033)
86. Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, et al. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature. 2008;453 (7197):948-51. (Pubitemid 351832561)
87. Reddy KL, Zullo JM, Bertolino E, Singh H. Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature. 2008;452(7184):243-7. (Pubitemid 351380248)
88. Ferrai C, Xie SQ, Luraghi P, Munari D, Ramirez F, Branco MR, et al. Poised transcription factories prime silent uPA gene prior to activation. PLoS Biol. 2010;8(1):e1000270.
89. Ramirez-Carrozzi VR, Braas D, Bhatt DM, Cheng CS, Hong C, Doty KR, et al. A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell. 2009;138(1):114-28.
90. Radonjic M. Andrau JC, Lijnzaad P, Kemmeren P, Kockelkorn TT, van Leenen D, et al. Genome-wide analyses reveal RNA polymerase II located upstream of genes poised for rapid response upon S cerevisiae stationary phase exit Mol Cell. 2005;18(2):171-83.
91. Boehm AK, Saunders A, Werner J, Lis JT. Transcription factor and polymerase recruitment, modification, and movement on dhsp70 in vivo in the minutes following heat shock. Mol Cell Biol. 2003;23(21):7628-37. (Pubitemid 37271461)
92. Booy EP, Henson ES, Gibson SB. Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer. Oncogene. 2010;30(20):2367-78.
93. Zeisel A, Kostler WJ, Molotski N, Tsai JM, Krauthgamer R, Jacob-Hirsch J, et al. Coupled pre-mRNA and mRNA dynamics unveil operational strategies underlying transcriptional responses to stimuli. Mol Syst Biol. 2011;7:529.
94. Shalem O, Dahan O, Levo M, Martinez MR, Furman I, Segal E, et al. Transient transcriptional responses to stress are generated by opposing effects of mRNA production and degradation. Mol Syst Biol. 2008;4223.
95. Brengues M, Teixeira D, Parker R. Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science. 2005;310(5747):486-9. (Pubitemid 41507961)
96. Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W. Stress-induced reversal of microRNA repression and mRNA Pbody localization in human cells. Cold Spring Harb Symp Quant Biol. 2006;71513-521.
97. Franks TM, Lykke-Andersen J. TTP and BRF proteins nucleate processing body formation to silence mRNAs with AU-rich elements. Genes Dev. 2007;21(6):719-35. (Pubitemid 46440293)
98. Jakymiw A, Lian S, Eystathioy T, Li S, Satoh M, Hamel JC, et al. Disruption of GW bodies impairs mammalian RNA interference. Nat Cell Biol. 2005;7(12):1267-74.
99. Piques M, SchulzeWX, Hohne M, Usadel B, Gibon Y, Rohwer J, et al. Ribosome and transcript copy numbers, polysome occupancy and enzyme dynamics in Arabidopsis. Mol Syst Biol. 2009;5314.
100. Staber PB, Vesely P, Haq N, Ott RG, Funato K, Bambach I, et al. The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling. Blood. 2007;110(9):3374-83. (Pubitemid 350106332)
101. Zwang Y, Sas-Chen A, Drier Y, Shay T, Avraham R, Lauriola M, et al. Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals. Mol Cell. 2011;42(4):524-35.
102. Pines G, Huang PH, Zwang Y, White FM, Yarden Y. EGFRvIV: a previously uncharacterized oncogenic mutant reveals a kinase autoinhibitory mechanism. Oncogene. 2010;29(43):5850-60.
103. Nagane M, Coufal F, Lin H, Bogler O, Cavenee WK, Huang HJ. A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res. 1996;56 (21):5079-86. (Pubitemid 26374452)
104. Li Y,Wang F, Lee JA, Gao FB. MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila. Genes Dev. 2006;20(20):2793-805. (Pubitemid 44771742)
105. Herranz H, Cohen SM. MicroRNAs and gene regulatory networks: managing the impact of noise in biological systems. Genes Dev. 2010;24(13):1339-44.
106. Tarcic G, Avraham R, Pines G, Amit I, Shay T, Lu Y, et al. EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF. Faseb J. 2011.