title: Focal adhesion kinase regulates expression of thioredoxin-interacting protein (TXNIP) in cancer cells.
abstract: Focal Adhesion Kinase (FAK) plays an important role in cancer cell survival. Previous microarray gene profiling study detected inverse regulation between expression of thioredoxin-interacting protein (TXNIP) and FAK, where down-regulation of FAK by siRNA in MCF-7 cells caused up-regulation of TXNIP mRNA level, and in contrast up-regulation of doxycyclin- induced FAK caused repression of TXNIP. In the present report, we show that overexpression of FAK in MCF-7 cells repressed TXNIP promoter activity. Treatment of MCF-7 cells with 1alpha, 25-dihydroxyvitamin D3 (1,25D) down-regulated endogenous FAK and up-regulated TXNIP protein level, and treatment with 5-FU decreased FAK protein expression and up-regulated TXNIP protein expression in 293 cells. Moreover, silencing of FAK with siRNA increased TXNIP protein expression, while overexpression of FAK inhibited TXNIP protein expression in 293 cells. In addition, treatment of DBTRG glioblastoma cells with FAK inhibitor Y15 increased TXNIP mRNA, decreased cancer cell viability and increased apoptosis. These results for the first time demonstrate FAK-regulated TXNIP expression which is important for apoptotic, survival and oxidative stress signaling pathways in cancer cells.
authors: Baotran
authors: B
authors: Ho
authors: Grace
authors: G
authors: Huang
authors: Department of Surgical Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA. Vita.Golubovskaya@roswellpark.org.
authors: Vita M
authors: VM
authors: Golubovskaya
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004318:Doxycycline / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C539551:1,2,4,5-benzenetetraamine; D000814:Aniline Compounds; D002352:Carrier Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C486715:TXNIP protein, human; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D051416:Focal Adhesion Protein-Tyrosine Kinases; D004318:Doxycycline; D005472:Fluorouracil
references: Immunity. 2005 Feb;22(2):195-208
references: 15723808
references: J Immunol. 2009 Aug 15;183(4):2495-505
references: 19625652
references: Melanoma Res. 2005 Oct;15(5):357-62
references: 16179862
references: Genes Cancer. 2010 Sep;1(9):893-907
references: 21779470
references: Am J Physiol Gastrointest Liver Physiol. 2010 Jul;299(1):G186-95
references: 20378826
references: J Immunol. 2000 Jun 15;164(12):6287-95
references: 10843682
references: Mol Biol Cell. 2001 Dec;12(12):4066-77
references: 11739801
references: Mol Endocrinol. 2001 Aug;15(8):1370-80
references: 11463860
references: Biochim Biophys Acta. 1994 Sep 13;1219(1):26-32
references: 8086474
references: Clin Cancer Res. 2000 Jun;6(6):2417-23
references: 10873094
references: Int J Cancer. 2009 Oct 1;125(7):1735-8
references: 19521985
references: Sci Signal. 2008 May 20;1(20):pe22
references: 18493017
references: BMC Cancer. 2009 Aug 12;9:280
references: 19671193
references: J Biol Chem. 2000 Sep 29;275(39):30597-604
references: 10899173
references: J Biol Chem. 2005 Jul 1;280(26):25008-21
references: 15855171
references: J Biol Chem. 2004 Jun 4;279(23):24387-93
references: 15047687
references: Bioessays. 1997 Feb;19(2):137-45
references: 9046243
references: Mol Cancer Ther. 2013 Feb;12(2):162-72
references: 23243059
references: Oncogene. 2003 Jun 26;22(26):4035-46
references: 12821938