title: JNK signaling maintains the mesenchymal properties of multi-drug resistant human epidermoid carcinoma KB cells through snail and twist1.
abstract: METHODS
  In addition to possess cross drug resistance characteristic, emerging evidences have shown that multiple-drug resistance (MDR) cancer cells exhibit aberrant metastatic capacity when compared to parental cells. In this study, we explored the contribution of c-Jun N-terminal kinases (JNK) signaling to the mesenchymal phenotypes and the aberrant motile capacity of MDR cells utilizing a well characterized MDR cell line KB/VCR, which is established from KB human epidermoid carcinoma cells by vincristine (VCR), and its parental cell line KB.
  
  
  RESULTS
  Taking advantage of experimental strategies including pharmacological tool and gene knockdown, we showed here that interference with JNK signaling pathway by targeting JNK1/2 or c-Jun reversed the mesenchymal properties of KB/VCR cells to epithelial phenotypes and suppressed the motile capacity of KB/VCR cells, such as migration and invasion. These observations support a critical role of JNK signaling in maintaining the mesenchymal properties of KB/VCR cells. Furthermore, we observed that JNK signaling may control the expression of both snail and twist1 in KB/VCR cells, indicating that both snail and twist1 are involved in controlling the mesenchymal characteristics of KB/VCR cells by JNK signaling.
  
  
  CONCLUSIONS
  JNK signaling is required for maintaining the mesenchymal phenotype of KB/VCR cells; and JNK signaling may maintain the mesenchymal characteristics of KB/VCR cells potentially through snail and twist1.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhan
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Feng
authors.forename: Ying
authors.initials: Y
authors.lastname: Kong
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Wenfu
authors.initials: W
authors.lastname: Tan
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D020935:MAP Kinase Signaling System; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D010641:Phenotype; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology
chemical_list: D015820:Cadherins; D009687:Nuclear Proteins; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D014746:Vimentin; D014750:Vincristine; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8
references.citation: Mol Cancer Res. 2010 Feb;8(2):266-77
references.pmid: 20145041
references.citation: J Biol Chem. 2009 May 8;284(19):12956-65
references.pmid: 19269969
references.citation: Nat Rev Cancer. 2005 Apr;5(4):275-84
references.pmid: 15803154
references.citation: Gastroenterology. 2011 May;140(5):1556-63.e6
references.pmid: 21320501
references.citation: Nat Rev Mol Cell Biol. 2006 Feb;7(2):131-42
references.pmid: 16493418
references.citation: Clin Exp Metastasis. 2009;26(3):197-204
references.pmid: 19112600
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13681-6
references.pmid: 11717429
references.citation: J Biol Chem. 2008 Nov 7;283(45):30549-56
references.pmid: 18757369
references.citation: Yao Xue Xue Bao. 1994;29(4):246-51
references.pmid: 7976338
references.citation: EMBO J. 2009 Jul 8;28(13):1843-54
references.pmid: 19521338
references.citation: J Biol Chem. 2006 Dec 22;281(51):39542-9
references.pmid: 17056591
references.citation: Blood. 2005 Aug 15;106(4):1382-91
references.pmid: 15890690
references.citation: Cell. 2008 May 16;133(4):704-15
references.pmid: 18485877
references.citation: Drug Resist Updat. 2003 Jun;6(3):147-56
references.pmid: 12860462
references.citation: J Clin Invest. 2009 Jun;119(6):1420-8
references.pmid: 19487818
references.citation: Oncogene. 2011 Dec 8;30(49):4874-86
references.pmid: 21625222
references.citation: Cancer Res. 2008 Jan 15;68(2):516-20
references.pmid: 18199547
references.citation: J Int Med Res. 2012;40(2):426-35
references.pmid: 22613403
references.citation: J Biol Chem. 2003 Jun 6;278(23):20582-92
references.pmid: 12663670
references.citation: Front Biosci. 2008 May 01;13:5138-54
references.pmid: 18508576
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13820-5
references.pmid: 19666588
references.citation: Cancer Res. 2009 Mar 15;69(6):2400-7
references.pmid: 19276344
references.citation: Genes Dev. 2011 Mar 15;25(6):634-45
references.pmid: 21406557
references.citation: J Clin Invest. 2009 Jun;119(6):1429-37
references.pmid: 19487819
references.citation: Dev Cell. 2008 Jun;14(6):818-29
references.pmid: 18539112
references.citation: Cell. 2009 Nov 25;139(5):871-90
references.pmid: 19945376
references.citation: Nat Rev Cancer. 2009 Aug;9(8):537-49
references.pmid: 19629069
references.citation: Oncogene. 2010 Aug 26;29(34):4741-51
references.pmid: 20531305
references.citation: Cancer Res. 2006 Nov 15;66(22):10902-10
references.pmid: 17108127
references.citation: BMC Cancer. 2010 May 20;10:219
references.pmid: 20487542
references.citation: Oncogene. 2010 Dec 2;29(48):6314-22
references.pmid: 20802532
references.citation: Cell. 2000 Oct 13;103(2):239-52
references.pmid: 11057897
references.citation: Carcinogenesis. 2011 May;32(5):667-75
references.pmid: 21296766
references.citation: Cancer Res. 2001 Apr 1;61(7):2857-61
references.pmid: 11306458
references.citation: Cell Mol Life Sci. 2008 Oct;65(20):3145-67
references.pmid: 18581055
references.citation: Cancer Res. 2009 Jan 15;69(2):573-82
references.pmid: 19147571
references.citation: Cell. 2006 Nov 17;127(4):679-95
references.pmid: 17110329
references.citation: Clin Cancer Res. 2004 Dec 15;10(24):8266-74
references.pmid: 15623602
references.citation: Clin Cancer Res. 2009 Apr 15;15(8):2657-65
references.pmid: 19336515