Submitted on April 10, 2006
Accepted on September 13, 2006
Epigenetic regulation of Integrin-Linked Kinase expression depending on adhesion of gastric carcinoma cells
Yong-Bae Kim1, Sung-Yul Lee2, Sang-Kyu Ye3, and Jung Weon Lee4*
1 Department of Tumor Biology, Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea, Republic of
2 Department of Molecular and Clinical Oncology, Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea, Republic of
3 Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Korea, Republic of
4 Departments of Tumor Biology, and Molecular & Clinical Oncology, Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea, Republic of
* To whom correspondence should be addressed. E-mail: jwl{at}snu.ac.kr.
Cell adhesion to the extracellular matrix 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 TGF
1-mediated acetylations of histone H3 and Lys9 of H3 and levels of integrin-linked kinase (ILK) mRNA and protein, than 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 (Lys9-) acetylated H3. Meanwhile, adherent cells showed more associations between HDAC3, Ski, and MeCP2. Chromatin immunoprecipitations with anti-acetylated H3, Lys9-acetylated H3, or p300/CBP antibody resulted in more co-precipitated ILK promoter, with being correlated with enhanced ILK mRNA and protein levels, in suspended cells. Moreover, ILK expression inversely regulated cell adhesion to extracellular matrix proteins and its over-expression 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.
