The role of serum response factor in hepatocellular carcinoma: implications for disease progression.
Serum response factor (SRF) regulates transcription of the immediate early genes and triggers proliferation, migration and differentiation in several types of cells. We examined the role of SRF in HCC by transfecting the SRF cDNA in HLE cells and the SRF anti-sense cDNA in sarcomatoid HCC cells. The overexpression of SRF in the HLE cells significantly increased the cell growth and proliferation. Overexpression of SRF increased actin polymerization of the HCC cells and induced morphologic changes. The mesenchymal markers vimentin, N-cadherin and RhoA were highly expressed in the SRF-transfected HLE cells. Furthermore, the overexpression of SRF in the HLE cells increased the expression levels of the active form of the beta-catenin and Wnt/beta-catenin target genes, such as c-myc and cyclin D1. The overexpression of SRF significantly enhanced the cell migration and invasiveness of HCC cells. Conversely, inhibition of the SRF expression in the sarcomatoid SH-J1 cells by the SRF anti-sense cDNA significantly decreased migration and invasion through the attenuated expression of mesenchymal markers and the proteins involved in the Wnt/beta-catenin pathway. These results indicate that the overexpression of SRF in HCC cells modulates the Wnt/beta-catenin pathway, and this plays an important role in HCC progression.
Kwon
Chang Young
CY
Department of Pathology, Chonbuk National University, Medical School, Institute for Medical Sciences, Research Institute of Clinical Medicine, Jeonju, Chonbuk 561-756, Korea.
Kim
Kyung Ryoul
KR
Choi
Ha Na
HN
Chung
Myoung Ja
MJ
Noh
Sang Jae
SJ
Kim
Dae Ghon
DG
Kang
Myoung Jae
MJ
Lee
Dong Geun
DG
Moon
Woo Sung
WS
D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D017781:Genes, Immediate-Early; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014746:Vimentin / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; C050361:CDH2 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; C476858:SRF protein, human; D026362:Serum Response Factor; D014746:Vimentin; D051153:Wnt Proteins; D051176:beta Catenin; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein