title: Epithelial-to-mesenchymal transition in breast cancer: a role for insulin-like growth factor I and insulin-like growth factor-binding protein 3?
abstract: Evidence indicates that for most human cancers the problem is not that gene mutations occur but is more dependent upon how the body deals with damaged cells. It has been estimated that only about 1% of human cancers can be accounted for by unmistakable hereditary cancer syndromes, only up to 5% can be accounted for due to high-penetrance, single-gene mutations, and in total only 5%-15% of all cancers may have a major genetic component. The predominant contribution to the causation of most sporadic cancers is considered to be environmental factors contributing between 58% and 82% toward different cancers. A nutritionally poor lifestyle is associated with increased risk of many cancers, including those of the breast. As nutrition, energy balance, macronutrient composition of the diet, and physical activity levels are major determinants of insulin-like growth factor (IGF-I) bioactivity, it has been proposed that, at least in part, these increases in cancer risk and progression may be mediated by alterations in the IGF axis, related to nutritional lifestyle. Localized breast cancer is a manageable disease, and death from breast cancer predominantly occurs due to the development of metastatic disease as treatment becomes more complicated with poorer outcomes. In recent years, epithelial-to-mesenchymal transition has emerged as an important contributor to breast cancer progression and malignant transformation resulting in tumor cells with increased potential for migration and invasion. Furthermore, accumulating evidence suggests a strong link between components of the IGF pathway, epithelial-to-mesenchymal transition, and breast cancer mortality. Here, we highlight some recent studies highlighting the relationship between IGFs, IGF-binding protein 3, and epithelial-to-mesenchymal transition.
authors: IGFs and Metabolic Endocrinology Group, School of Clinical Sciences, University of Bristol, Learning and Research Building, Southmead Hospital, Bristol, UK.
authors: Hanna A
authors: HA
authors: Zielinska
authors: Department of Clinical Oncology, Bristol Haematology and Oncology Centre, University Hospitals Bristol, Bristol, UK.
authors: Amit
authors: A
authors: Bahl
authors: IGFs and Metabolic Endocrinology Group, School of Clinical Sciences, University of Bristol, Learning and Research Building, Southmead Hospital, Bristol, UK.
authors: Jeff Mp
authors: JM
authors: Holly
authors: IGFs and Metabolic Endocrinology Group, School of Clinical Sciences, University of Bristol, Learning and Research Building, Southmead Hospital, Bristol, UK.
authors: Claire M
authors: CM
authors: Perks
keywords: EMT; IGF-I; IGFBP-3; breast cancer
references: J Biol Chem. 1996 May 17;271(20):11641-5
references: 8662806
references: Int J Cancer. 1996 Mar 15;65(6):812-20
references: 8631597
references: J Biol Chem. 1994 Nov 18;269(46):28783-9
references: 7961833
references: Endocrinology. 1995 Apr;136(4):1635-41
references: 7895674
references: Cancer Res. 1999 Aug 1;59(15):3588-91
references: 10446966
references: J Biol Chem. 1994 May 13;269(19):13779-84
references: 7514593
references: J Biol Chem. 2011 Apr 8;286(14 ):12024-32
references: 21317430
references: Cancer Res. 1999 Nov 15;59(22):5692-4
references: 10582686
references: Oncology (Williston Park). 2011 May;25(6):535-6; discussion 551
references: 21717908
references: Clin Cancer Res. 2005 Feb 1;11(3):1154-9
references: 15709183
references: J Biol Chem. 1998 Apr 24;273(17):10726-32
references: 9553137
references: Cancer Res. 1996 Jul 15;56(14):3165-7
references: 8764099
references: Pediatr Nephrol. 2000 Jul;14(7):558-61
references: 10912518
references: J Biol Chem. 2010 Dec 10;285(50):38788-800
references: 20851879
references: Oncogene. 2011 Nov 24;30(47):4707-20
references: 21602879
references: Clin Cancer Res. 1997 Jan;3(1):103-9
references: 9815544
references: Curr Biol. 2009 Aug 11;19(15):R657-66
references: 19674551
references: Endocr Relat Cancer. 2010 May 18;17(2):539-51
references: 20356977
references: Mol Cell Biol. 1999 May;19(5):3278-88
references: 10207053
references: Eur J Biochem. 1994 Jul 1;223(1):195-202
references: 8033892
references: Endocr Relat Cancer. 2006 Jun;13(2):583-92
references: 16728584
references: Biomark Cancer. 2013 Oct 29;5:61-70
references: 24250234
references: J Clin Oncol. 2008 Sep 1;26(25):4072-7
references: 18757321
references: J Biol Chem. 1997 Oct 10;272(41):25602-7
references: 9325280
references: Br J Cancer. 2002 Jun 17;86(12):1963-9
references: 12085194
references: Br J Cancer. 1992 Aug;66(2):248-53
references: 1323990
references: Lancet Oncol. 2010 Jun;11(6):530-42
references: 20472501
references: Cell Death Dis. 2013 Oct 24;4:e875
references: 24157869
references: Cell Commun Signal. 2011 May 02;9(1):10
references: 21535875
references: J Clin Invest. 2009 Jun;119(6):1420-8
references: 19487818
references: Cancer Epidemiol Biomarkers Prev. 2004 Nov;13(11 Pt 1):1759-64
references: 15533904
references: Mol Cell Biol. 1999 Oct;19(10):7203-15
references: 10490655
references: J Biol Chem. 1998 Mar 20;273(12):7162-8
references: 9507031
references: Nat Cell Biol. 2009 Aug;11(8):943-50
references: 19597490
references: J Cell Biochem. 1999 Dec 15;75(4):652-64
references: 10572248
references: Endocrinology. 1990 Dec;127(6):2679-86
references: 1701124
references: J Biol Chem. 2001 Jul 13;276(28):26699-707
references: 11323435
references: Cancer Res. 2002 Jan 15;62(2):497-505
references: 11809701
references: J Cell Sci. 2011 May 15;124(Pt 10):1752-8
references: 21525039
references: Growth Horm IGF Res. 2008 Dec;18(6):487-96
references: 18502161
references: J Clin Endocrinol Metab. 1993 Nov;77(5):1246-50
references: 7521344
references: J Cell Biol. 2005 Dec 19;171(6):1023-34
references: 16365168
references: Biochim Biophys Acta. 2013 Dec;1836(2):345-53
references: 24189571
references: Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):763-8
references: 17416768
references: Prog Growth Factor Res. 1995;6(2-4):513-20
references: 8817696
references: PLoS One. 2013 Apr 12;8(4):e60471
references: 23593224
references: Ecancermedicalscience. 2013 Aug 23;7:343
references: 23983815
references: Clin Oncol (R Coll Radiol). 2010 May;22(4):281-8
references: 20189371
references: J Hematol Oncol. 2014 Mar 05;7:19
references: 24598126
references: Cancer Res. 2008 Apr 1;68(7):2479-88
references: 18381457
references: Cancer Res. 2007 Dec 15;67(24):11721-31
references: 18089802
references: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10069-74
references: 17537911
references: J Clin Pathol. 1997 Feb;50(2):135-7
references: 9155694
references: Neuro Oncol. 1999 Apr;1(2):109-19
references: 11550306
references: Nat Rev Cancer. 2014 May;14(5):329-41
references: 24722429
references: Eur J Endocrinol. 2009 Apr;160(4):695-703
references: 19176646
references: Lancet. 2004 Apr 24;363(9418):1346-53
references: 15110491
references: Cell. 2008 May 16;133(4):704-15
references: 18485877
references: Oncogene. 1999 Apr 15;18(15):2471-9
references: 10229198
references: Crit Rev Oncog. 2012;17(2):161-73
references: 22471706
references: Oncologist. 2014 Aug;19(8):805-13
references: 24969162
references: Growth Horm IGF Res. 2014 Oct;24(5):164-73
references: 24953254
references: Int J Cancer. 2000 Nov 1;88(3):336-41
references: 11054660
references: Breast Cancer Res Treat. 2010 Sep;123(2):333-44
references: 20204498
references: Endocr Rev. 1995 Apr;16(2):143-63
references: 7540132
references: Pediatr Endocrinol Rev. 2005 Sep;3(1):11-9
references: 16369209
references: J Biol Chem. 1993 Jul 15;268(20):14964-71
references: 7686909
references: Oncology. 1998 May-Jun;55(3):242-8
references: 9560057
references: Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(8):314-23
references: 19838011
references: Carcinogenesis. 2010 Jan;31(1):83-9
references: 19969554
references: J Cell Sci. 2002 Nov 15;115(Pt 22):4293-303
references: 12376561
references: Int J Cancer. 2014 Jun 1;134(11):2683-90
references: 24248481
references: J Biol Chem. 2002 Oct 18;277(42):39684-95
references: 12138094
references: Cancer Res. 2008 Feb 15;68(4):989-97
references: 18281472
references: Endocrinology. 2006 Jul;147(7):3484-500
references: 16614079
references: Breast Cancer Res Treat. 1997 Aug;45(1):81-95
references: 9285120
references: Horm Metab Res. 1999 Feb-Mar;31(2-3):242-6
references: 10226808
references: PLoS One. 2013 Sep 05;8(9):e73406
references: 24039934
references: Biomed Pharmacother. 2011 Feb;65(1):40-5
references: 21177063
references: Birth Defects Res C Embryo Today. 2003 Nov;69(4):257-71
references: 14745968
references: Curr Oncol. 2013 Aug;20(4):e283-8
references: 23904766
references: J Clin Invest. 2009 Jun;119(6):1429-37
references: 19487819
references: Cancer Res. 2000 Jan 1;60(1):22-7
references: 10646845
references: Carcinogenesis. 2011 Sep;32(9):1381-7
references: 21665891
references: Growth Horm IGF Res. 2012 Jun-Aug;22(3-4):108-15
references: 22551578
references: Mol Cell Biol. 2007 Apr;27(8):3165-75
references: 17296734
references: Endocrinology. 2001 Nov;142(11):4969-75
references: 11606465
references: Breast Cancer Res. 2005;7(1):R119-29
references: 15642160
references: Eur J Cancer. 2002 Dec;38(18):2362-70
references: 12460779
references: FEBS Lett. 1995 Oct 2;373(1):51-5
references: 7589433
references: Mol Cell Biol. 2012 May;32(10):1893-907
references: 22431524
references: Endocr Relat Cancer. 2013 Oct 24;20(6):R321-39
references: 24080445
references: J Mol Endocrinol. 1998 Feb;20(1):157-62
references: 9513092
references: Endocrinol Metab Clin North Am. 2012 Jun;41(2):249-63, v
references: 22682629
references: Development. 1991 Apr;111(4):983-92
references: 1879366
references: Sci Rep. 2012;2:785
references: 23139858
references: J Biol Chem. 1995 Jun 9;270(23):13589-92
references: 7539790
references: Chin J Cancer. 2013 May;32(5):242-52
references: 23601239
references: Cancer Med. 2012 Oct;1(2):275-88
references: 23342276
references: Mol Cell Biol. 2004 Jan;24(1):306-19
references: 14673164
references: Int J Cancer. 2000 Nov 1;88(3):448-53
references: 11054675
references: Mol Pathol. 2001 Jun;54(3):133-7
references: 11376123
references: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references: 12629218
references: Ann Oncol. 2012 Apr;23(4):860-6
references: 21821546
references: Exp Cell Res. 1998 Jan 10;238(1):116-21
references: 9457063
references: Exp Cell Res. 1999 Aug 25;251(1):244-55
references: 10438590
references: Int J Cancer. 2013 Mar 1;132(5):1191-200
references: 22847383
references: Breast Cancer Res. 2009;11(4):R46
references: 19589136
references: Int J Cancer. 1998 Dec 18;79(6):624-8
references: 9842972
references: Am J Physiol. 1998 Jul;275(1 Pt 1):E55-63
references: 9688874
references: FEBS J. 2013 May;280(10):2248-59
references: 23374155
references: J Biol Chem. 1999 Feb 26;274(9):5422-8
references: 10026153
references: Oncologist. 2005;10 Suppl 3:20-9
references: 16368868
references: Oncogene. 1999 Jul 15;18(28):4063-8
references: 10435587
references: Int J Cancer. 2003 Aug 10;106(1):90-5
references: 12794762
references: Curr Opin Oncol. 2005 Jan;17(1):49-54
references: 15608513
references: Clin Cancer Res. 1999 Jul;5(7):1935-44
references: 10430101
references: J Biol Chem. 1999 Aug 20;274(34):24408-16
references: 10446221
references: Endocrinology. 2002 Oct;143(10):3711-4
references: 12239079
references: Cancer Cell. 2005 Sep;8(3):197-209
references: 16169465
references: Breast Cancer Res Treat. 1998 Feb;47(3):269-81
references: 9516081
references: Science. 2013 Feb 1;339(6119):580-4
references: 23372014
references: Oncogene. 2013 Jun 27;32(26):3130-8
references: 22824790
references: Cell. 1992 Jul 10;70(1):93-104
references: 1623525
references: Oncogene. 1995 May 4;10(9):1725-9
references: 7753549
references: Nat Rev Cancer. 2002 Jun;2(6):442-54
references: 12189386
references: Cancer Res. 1993 Aug 15;53(16):3736-40
references: 8339284