title: IBP regulates epithelial-to-mesenchymal transition and the motility of breast cancer cells via Rac1, RhoA and Cdc42 signaling pathways.
abstract: Epithelial-to-mesenchymal transition (EMT) is a crucial process for the invasion and metastasis of epithelial tumors. However, the molecular mechanisms underlying this transition are poorly understood. In this study, we demonstrate that interferon regulatory factor 4 binding protein (IBP) regulates EMT and the motility of breast cancer cells through Rac1, RhoA and Cdc42 signaling pathways. We found that increased expression of IBP was associated with the progression of breast cancer and that IBP protein levels were significantly elevated in matched distant metastases. High IBP levels also predict shorter overall survival of breast cancer patients. Furthermore, the forced expression of IBP decreased the expression of the epithelial marker E-cadherin but increased the mesenchymal markers in breast cancer cells. In contrast, silencing IBP in metastatic breast tumor cells promoted a shift toward an epithelial morphology concomitant with increased expression of E-cadherin and decreased expression of mesenchymal markers. IBP silencing also reduced the expression of EMT-inducing transcription factors (Snail, Slug, ZEB1 and ZEB2). Moreover, we identified a role for IBP in endogenous EMT induced by epidermal growth factor (EGF) and deletion of IBP attenuated EGF receptor (EGFR) signaling in breast cancer cells. Furthermore, IBP regulates the migration, invasion and matrix metalloprotease production in breast cancer cells as well as actin cytoskeleton rearrangement and the activation of GTP-Rac1, GTP-RhoA and GTP-Cdc42. Taken together, our findings demonstrate an oncogenic property for IBP in promoting the metastatic potential of breast cancer cells.
authors: Department of Clinical Biochemistry, Faculty of Medical Laboratory Science, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Z
authors: Z
authors: Zhang
authors: Department of Clinical Biochemistry, Faculty of Medical Laboratory Science, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: M
authors: M
authors: Yang
authors: Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: R
authors: R
authors: Chen
authors: Department of Medical Laboratory, Beibei Maternal and Child Health Hospital, Chongqing, China.
authors: W
authors: W
authors: Su
authors: Department of Clinical Biochemistry, Faculty of Medical Laboratory Science, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: P
authors: P
authors: Li
authors: Department of Clinical Biochemistry, Faculty of Medical Laboratory Science, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: S
authors: S
authors: Chen
authors: Department of Clinical Biochemistry, Faculty of Medical Laboratory Science, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Z
authors: Z
authors: Chen
authors: Department of Clinical Biochemistry, Faculty of Medical Laboratory Science, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: A
authors: A
authors: Chen
authors: Department of Clinical Biochemistry, Faculty of Medical Laboratory Science, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: S
authors: S
authors: Li
authors: Department of Clinical Biochemistry, Faculty of Medical Laboratory Science, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: C
authors: C
authors: Hu
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D004815:Epidermal Growth Factor / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D050835:Interferon Regulatory Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; D020764:cdc42 GTP-Binding Protein / Q000096:biosynthesis*; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis*; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis*; D000099218:Interferon Regulatory Factor-4
chemical_list: D015820:Cadherins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D018398:Homeodomain Proteins; D050835:Interferon Regulatory Factors; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D000099218:Interferon Regulatory Factor-4; C107953:RAC1 protein, human; C000604407:SNAI1 protein, human; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; C066737:RHOA protein, human; C512478:EGFR protein, human
references: Oncogene. 2005 Nov 14;24(50):7443-54
references: 16288291
references: Clin Exp Metastasis. 2008;25(6):685-93
references: 18236164
references: J Natl Cancer Inst. 1993 Feb 3;85(3):200-6
references: 8423624
references: Cancer Epidemiol. 2009 Aug;33(2):130-6
references: 19679060
references: Immunity. 2008 Nov 14;29(5):704-19
references: 18976935
references: Science. 1998 Jan 23;279(5350):509-14
references: 9438836
references: J Biol Chem. 2012 Sep 7;287(37):31073-84
references: 22829599
references: J Clin Invest. 2007 Aug;117(8):2164-75
references: 17657315
references: J Clin Invest. 2006 Mar;116(3):703-14
references: 16470246
references: J Biol Chem. 2007 Jan 19;282(3):2011-8
references: 17121847
references: Cancer Metastasis Rev. 2009 Jun;28(1-2):15-33
references: 19169796
references: J Biol Chem. 2007 May 25;282(21):15730-42
references: 17403664
references: Immunity. 2003 Mar;18(3):403-14
references: 12648457
references: J Immunol. 2009 Dec 1;183(11):7259-67
references: 19915062
references: BMC Cancer. 2009 Jul 15;9:235
references: 19604397
references: Cancer Invest. 2012 Dec;30(10):748-56
references: 23088770
references: Int Immunopharmacol. 2009 Jul;9(7-8):1002-9
references: 19393345
references: FEBS Lett. 2008 Jun 18;582(14):2093-101
references: 18460342
references: Br J Haematol. 1999 Aug;106(2):335-44
references: 10460589
references: Oncogene. 2008 Nov 24;27(55):6958-69
references: 19029937
references: Exp Cell Res. 2004 Apr 1;294(2):335-44
references: 15023524
references: Hum Immunol. 2003 Apr;64(4):389-401
references: 12651066
references: Nat Rev Cancer. 2002 Jun;2(6):442-54
references: 12189386
references: Ann Oncol. 2007 Oct;18(10):1605-19
references: 17355951
references: J Mammary Gland Biol Neoplasia. 2010 Jun;15(2):191-9
references: 20369376
references: Mol Cancer. 2012 Aug 13;11:54
references: 22888789
references: Cancer Res. 2007 Oct 1;67(19):9066-76
references: 17909010
references: Oncogene. 2012 Oct 25;31(43):4619-29
references: 22249256
references: Small GTPases. 2012 Oct-Dec;3(4):225-8
references: 22735340