Role of cell adhesion signal molecules in hepatocellular carcinoma cell apoptosis.
OBJECTIVE
Cell adhesion molecules and their signal molecules play a very important role in carcinogenesis. The aim of this study is to elucidate the role of these molecules and the signal molecules of integrins and E-cadherins, such as (focal adhesion kinase) FAK, (integrin linked kinase) ILK, and beta-catenin in hepatocellular carcinoma cell apoptosis.


METHODS
We first synthesized the small molecular compound, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and identified it, by element analysis and (1)H NMR. To establish the apoptosis model of the SMMC-7721 hepatocellular carcinoma cell, we treated cells with DCVC in EBSS for different concentrations or for various length times in the presence of 20 micromol/L N,N'-diphenyl-p-phenylenediamine, which blocks necrotic cell death and identified this model by flow cytometry and DNA ladder. Then we studied the changes of FAK, ILK, beta-catenin, and PKB in this apoptotic model by Western blot.


RESULTS
We found that the loss or decrease of cell adhesion signal molecules is an important reason in apoptosis of SMMC-7721 hepatocellular carcinoma cell and the apoptosis of SMMC-7721 cell was preceded by the loss or decrease of FAK, ILK, PKB, and beta-catenin or the damage of cell-matrix and cell-cell adhesion.


CONCLUSIONS
Our results suggested that the decrease of adhesion signal molecules, FAK, ILK, PKB, and beta-catenin, could induce hepatocellular carcinoma cell apoptosis.
Su
Jian-Min
JM
Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, China.
Wang
Li-Ying
LY
Liang
Yu-Long
YL
Zha
Xi-Liang
XL
D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin; D000099200:Scaffold Protein ILK
D015815:Cell Adhesion Molecules; D003545:Cysteine; D003598:Cytoskeletal Proteins; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D015534:Trans-Activators; D051176:beta Catenin; D000099200:Scaffold Protein ILK; C495270:CTNNB1 protein, human; C039961:S-(1,2-dichlorovinyl)cysteine; C496050:PTK2 protein, human