Epigenetic regulation of integrin-linked kinase expression depending on adhesion of gastric carcinoma cells.
Cell adhesion to the extracellular matrix (ECM) regulates gene expressions in diverse dynamic environments. However, the manner in which gene expressions are regulated by extracellular cues is largely unknown. In this study, suspended gastric carcinoma cells showed higher basal and transforming growth factor-beta1 (TGFbeta1)-mediated acetylations of histone 3 (H3) and Lys(9) of H3 and levels of integrin-linked kinase (ILK) mRNA and protein than did fibronectin-adherent cells did. Moreover, the insignificant acetylation and ILK expression in adherent cells were recovered by alterations of integrin signaling and actin organization, indicating a connection between cytoplasmic and nuclear changes. Higher acetylations in suspended cells were correlated with associations between Smad4, p300/CBP, and Lys(9)-acetylated H3. Meanwhile, adherent cells showed more associations between HDAC3, Ski, and MeCP2. Chromatin immunoprecipitations with anti-acetylated H3, Lys(9)-acetylated H3, or p300/CBP antibody resulted in more coprecipitated ILK promoter, correlated with enhanced ILK mRNA and protein levels, in suspended cells. Moreover, ILK expression inversely regulated cell adhesion to ECM proteins, and its overexpression enhanced cell growth in soft agar. These observations indicate that cell adhesion and/or its related molecular basis regulate epigenetic mechanisms leading to a loss of ILK transcription, which in turn regulates cell adhesion property in a feedback linkage.
Kim
Yong-Bae
YB
Cancer Research Institute, Depts. of Tumor Biology and Molecular and Clinical Oncology, College of Medicine, Seoul National Univ., Seoul 110-799, Korea.
Lee
Sung-Yul
SY
Ye
Sang-Kyu
SK
Lee
Jung Weon
JW
D000107:Acetylation; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D044127:Epigenesis, Genetic; D005353:Fibronectins / Q000502:physiology; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099200:Scaffold Protein ILK; D000099186:Histone Deacetylase 3
D004268:DNA-Binding Proteins; D005353:Fibronectins; D006655:Histone Deacetylases; D006657:Histones; D051783:Methyl-CpG-Binding Protein 2; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051901:Smad4 Protein; D053773:Transforming Growth Factor beta1; D050880:p300-CBP Transcription Factors; D000099200:Scaffold Protein ILK; D000099186:Histone Deacetylase 3; C497392:MECP2 protein, human; C497796:SMAD4 protein, human; C060614:SKI protein, human