title: FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial-to-mesenchymal transition in human lung cancers.
abstract: The forkhead box transcription factor A2 (FOXA2) is an important regulator in animal development and body homeostasis. However, whether FOXA2 is involved in transforming growth factor β1 (TGF-β1)-mediated epithelial-to-mesenchymal transition (EMT) and tumor metastasis remains unknown. The present study showed that in human lung cancer cell lines, the abundance of FOXA2 positively correlates with epithelial phenotypes and negatively correlates with the mesenchymal phenotypes of cells, and TGF-β1 treatment decreased FOXA2 protein level. Consistently, knockdown of FOXA2 promoted EMT and invasion of lung cancer cells, whereas overexpression of FOXA2 reduced the invasion and suppressed TGF-β1-induced EMT. In addition, knockdown of FOXA2 induced slug expression, and ectopic expression of FOXA2 inhibited slug transcription. Furthermore, we identified that FOXA2 can bind to slug promoter through a conserved binding site, and that the DNA-binding region and transactivation region II of FOXA2 are required for repression of the slug promoter. These data demonstrate that FOXA2 functions as a suppressor of tumor metastasis by inhibition of EMT.
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yunneng
authors.initials: Y
authors.lastname: Tang
authors.forename: Guangwen
authors.initials: G
authors.lastname: Shu
authors.forename: Xinwang
authors.initials: X
authors.lastname: Yuan
authors.forename: Naihe
authors.initials: N
authors.lastname: Jing
authors.forename: Jianguo
authors.initials: J
authors.lastname: Song
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: C496502:FOXA2 protein, human; D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D051542:Hepatocyte Nuclear Factor 3-beta
references.citation: Cell Death Differ. 2003 May;10(5):516-27
references.pmid: 12728250
references.citation: Cancer Res. 2010 Mar 1;70(5):2115-25
references.pmid: 20160041
references.citation: Cell Metab. 2006 Feb;3(2):99-110
references.pmid: 16459311
references.citation: J Cell Biol. 1997 Jun 16;137(6):1403-19
references.pmid: 9182671
references.citation: Cancer Res. 2009 Sep 15;69(18):7180-7
references.pmid: 19738073
references.citation: Cell. 2009 Nov 25;139(5):871-90
references.pmid: 19945376
references.citation: Mol Biol Cell. 2008 Nov;19(11):4875-87
references.pmid: 18799618
references.citation: Cancer Res. 2002 Mar 15;62(6):1613-8
references.pmid: 11912130
references.citation: Cell. 2008 Apr 4;133(1):66-77
references.pmid: 18394990
references.citation: Curr Opin Cell Biol. 2009 Apr;21(2):166-76
references.pmid: 19237272
references.citation: Dev Biol. 1995 Nov;172(1):86-99
references.pmid: 7589816
references.citation: Development. 2009 Mar;136(6):1029-38
references.pmid: 19234065
references.citation: Cancer Sci. 2007 Oct;98(10):1512-20
references.pmid: 17645776
references.citation: Respir Res. 2005 Jun 09;6:56
references.pmid: 15946381
references.citation: Hum Pathol. 2004 May;35(5):560-4
references.pmid: 15138929
references.citation: Nature. 2008 Mar 13;452(7184):187-93
references.pmid: 18337816
references.citation: Nat Rev Mol Cell Biol. 2006 Feb;7(2):131-42
references.pmid: 16493418
references.citation: Oncogene. 2006 Nov 23;25(55):7235-44
references.pmid: 16799646
references.citation: Mol Cell Biol. 1994 Apr;14(4):2755-66
references.pmid: 8139574
references.citation: Nat Med. 2006 Jan;12(1):38-9
references.pmid: 16397559
references.citation: Mol Cell Biol. 1992 Sep;12(9):3723-32
references.pmid: 1324404
references.citation: Genes Dev. 2009 Apr 1;23(7):804-9
references.pmid: 19339686
references.citation: Cancer Res. 2009 Jul 1;69(13):5340-8
references.pmid: 19531652
references.citation: FASEB J. 2007 May;21(7):1445-62
references.pmid: 17283222
references.citation: Cancer Res. 2000 Sep 1;60(17):4894-906
references.pmid: 10987304
references.citation: J Cell Biol. 2007 Dec 3;179(5):1027-42
references.pmid: 18056415
references.citation: Cancer Res. 2009 Sep 15;69(18):7135-9
references.pmid: 19738043
references.citation: Nucleic Acids Res. 1995 Apr 11;23(7):1184-91
references.pmid: 7739897
references.citation: Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7628-31
references.pmid: 7689224
references.citation: Nat Med. 2008 Aug;14(8):828-36
references.pmid: 18660816
references.citation: Curr Opin Cell Biol. 2005 Oct;17(5):548-58
references.pmid: 16098727
references.citation: Int J Oncol. 2004 Nov;25(5):1495-500
references.pmid: 15492844
references.citation: Cell Mol Life Sci. 2006 Oct;63(19-20):2317-28
references.pmid: 16909212
references.citation: Lancet Oncol. 2001 Sep;2(9):533-43
references.pmid: 11905707
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 5;101(40):14449-54
references.pmid: 15452354
references.citation: Br J Cancer. 2006 Jun 19;94(12):1816-22
references.pmid: 16773075
references.citation: Antioxid Redox Signal. 2010 Jun 15;12(12):1383-430
references.pmid: 19903090