Butyrate regulates the expression of c-Src and focal adhesion kinase and inhibits cell invasion of human colon cancer cells.
Epidemiological studies indicate that dietary fiber-derived fermentation products such as butyrate can prevent colon cancer development. To further dissect the role of butyrate in anticarcinogenesis, its effect on cellular growth and invasion as well as the expression of c-Src and FAK, two mutually interactive nonreceptor tyrosine kinases, in three different human colon cancer cell lines (Caco-2, SW480, and SW620) were investigated. In addition to growth inhibition, butyrate treatment results in a significant downregulation of c-Src and FAK in human colon cancer cells, which can be attributable to their reduced transcripts and implicates the participation of a butyrate-sensitive pathway in modulating their expression. Concurrent to butyrate-reduced c-Src and FAK expression is the decrease of FAK Tyr-decrease 397 phosphorylation. Besides, butyrate also abolished the secretion of MMP-2 and MMP-9. And these butyrate-mediated effects severely impaired invasion of SW620 cells through Matrigel in vitro. Interestingly, in situ parallel enhancement of c-Src and FAK was also observed in human colorectal tumor specimens. These results imply that by virtue of suppression of c-Src and FAK along with other butyrate targets in colonocytes, butyrate could effectively inhibit tumor growth and invasion.
Lee
Jenq-Chang
JC
Department of Surgery, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Maa
Ming-Chei
MC
Yu
Hsiu-Shan
HS
Wang
Jung-Hui
JH
Yen
Chia-Kuang
CK
Wang
Shan-Tair
ST
Chen
Yen-Jen
YJ
Liu
Yuan
Y
Jin
Ying-Tai
YT
Leu
Tzeng-Horng
TH
D000107:Acetylation / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D002087:Butyrates; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9