Novel effects of SPHINGOSYLPHOSPHORYLCHOLINE (cas 1670-26-4) on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to WNT activation

Add time:09/27/2019    Source:sciencedirect.com

SPHINGOSYLPHOSPHORYLCHOLINE (cas 1670-26-4) (SPC) participates in several cellular processes including metastasis. SPC induces keratin reorganization and regulates the viscoelasticity of metastatic cancer cells including PANC-1 cancer cells leading to enhanced migration and invasion. The role of SPC and the relevant mechanism in invasion of breast cell are as yet unknown. SPC dose-dependently induces invasion of breast cancer cells or breast immortalized cells. Reverse transcription polymerase chain reaction and Western blot analyses of MCF10A and ZR-75-1 cells indicated that SPC induces expression and secretion of matrix metalloproteinase-3 (MMP3). From online KMPLOT, relapse free survival is high in patients having low MMP3 expressed basal breast cancer (n = 581, p = 0.032). UK370106 (MMP3 inhibitor) or gene silencing of MMP3 markedly inhibited the SPC-induced invasion of MCF10A cells. An extracellular signal-regulated kinase (ERK) inhibitor, PD98059, significantly suppressed the secretion and the gelatinolytic activity of MMP3, and invasion in MCF10A cells. Over-expression of ERK1 and ERK2 promoted both the expression and secretion of MMP3. In contrast, gene silencing of ERK1 and ERK2 attenuated the secretion of MMP3 in MCF10A cells. The effects of SPC-induced MMP3 secretion on β-catenin and TCF/lymphoid enhancer factor (LEF) promoter activity were examined since MMP3 indirectly activates canonical Wnt signaling. SPC induced translocation of β-catenin to nucleus and increased TCF/LEF promoter activity. These events were suppressed by UK370106 or PD98059. Wnt inhibitor, FH535 inhibited SPC-induced MMP3 secretion and invasion.Taken together, these results suggest that SPC induces MMP3 expression and secretion via ERK leading to Wnt activation.

We also recommend Trading Suppliers and Manufacturers of SPHINGOSYLPHOSPHORYLCHOLINE (cas 1670-26-4). Pls Click Website Link as below: cas 1670-26-4 suppliers

Prev:ReviewThe multi-functional role of SPHINGOSYLPHOSPHORYLCHOLINE (cas 1670-26-4)
Next:Short communicationThe critical micelle concentrations of lysophosphatidic acid and SPHINGOSYLPHOSPHORYLCHOLINE (cas 1670-26-4))