Inhibition of SPHK1 suppresses phorbol 12-myristate 13-acetate-induced metastatic phenotype in colorectal cancer HT-29 cells.
Expression of sphingosine kinase 1 (SPHK1) plays a role in colorectal cancer progression. This study aimed to demonstrate the mechanism of human colorectal cancer cell metastatic phenotype through SPHK1 knockdown. Human colorectal cancer HT-29 cells were stimulated by phorbol 12-myristate 13-acetate (PMA) with or without SPHK1 siRNA transfection. Tumor cell phenotypic changes were analyzed by using invasion, motility, cell viability, and apoptosis assays. Gene expressions were assessed using Western blot. PMA induced a metastatic phenotype in colorectal cancer cells, as indicated by cell viability, migration and invasion capacity, and ERK1/2 phosphorylation, whereas SPHK1 siRNA transfection suppressed the metastatic phenotype of tumor cells and antagonized PMA's effects. SPHK1 knockdown also inhibited secretion of MMP-2 and MMP-9 into the tumor cell conditioned medium. Suppression of SPHK1 expression suppresses the PMA-induced metastatic phenotype via ERK1/2 phosphorylation in human colorectal cancer cells.
Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Guangxi Zhuang Autonomous Region, China.
Meng-Bin
MB
Qin
Jie-An
JA
Huang
Shi-Quan
SQ
Liu
Guo-Du
GD
Tang
Hai-Xing
HX
Jiang
D017209:Apoptosis; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control* / Q000556:secondary; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects*; D000099157:Sphingosine Kinase
D002273:Carcinogens; D017853:Phosphotransferases (Alcohol Group Acceptor); D011493:Protein Kinase C; D034741:RNA, Small Interfering; D013755:Tetradecanoylphorbol Acetate; D000099157:Sphingosine Kinase