PMID- 27216977 OWN - NLM STAT- MEDLINE DCOM- 20190128 LR - 20190128 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1862 IP - 9 DP - 2016 Sep TI - Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to WNT activation. PG - 1533-43 LID - S0925-4439(16)30118-1 [pii] LID - 10.1016/j.bbadis.2016.05.010 [doi] AB - Sphingosylphosphorylcholine (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 beta-catenin and TCF/lymphoid enhancer factor (LEF) promoter activity were examined since MMP3 indirectly activates canonical Wnt signaling. SPC induced translocation of beta-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. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Kim, Hyun Ji AU - Kim HJ AD - BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 04620, Republic of Korea. FAU - Kang, Gyeoung Jin AU - Kang GJ AD - BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 04620, Republic of Korea. FAU - Kim, Eun Ji AU - Kim EJ AD - BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 04620, Republic of Korea. FAU - Park, Mi Kyung AU - Park MK AD - BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 04620, Republic of Korea. FAU - Byun, Hyun Jung AU - Byun HJ AD - BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 04620, Republic of Korea. FAU - Nam, Seungyoon AU - Nam S AD - Department of Life Sciences, College of BioNano Technology, Gachon University, Sungnam 13120, Republic of Korea. FAU - Lee, Ho AU - Lee H AD - National Cancer Center, Goyang-si, Gyeonggi-do 10408, Republic of Korea. FAU - Lee, Chang Hoon AU - Lee CH AD - BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 04620, Republic of Korea. Electronic address: uatheone@dongguk.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160520 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (3-(((2,2-dimethyl-1-(((2-methoxy-1-phenylethyl)amino)carbonyl)propyl)amino)carbonyl)-6-(3-methyl-4-phenylphenyl)hexanoic acid) RN - 0 (Caproates) RN - 0 (Flavonoids) RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (Polycyclic Compounds) RN - 10216-23-6 (sphingosine phosphorylcholine) RN - 107-73-3 (Phosphorylcholine) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - HG18B9YRS7 (Valine) RN - NGZ37HRE42 (Sphingosine) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Breast Neoplasms/*drug therapy/*metabolism/pathology MH - Caproates/pharmacology MH - Cell Line, Tumor MH - Female MH - Flavonoids/pharmacology MH - Gene Silencing MH - Humans MH - Matrix Metalloproteinase 3/genetics/*metabolism MH - Matrix Metalloproteinase Inhibitors/pharmacology MH - Neoplasm Invasiveness/pathology/physiopathology MH - Phosphorylcholine/*analogs & derivatives/metabolism/pharmacology MH - Polycyclic Compounds/pharmacology MH - Sphingosine/*analogs & derivatives/metabolism/pharmacology MH - Valine/analogs & derivatives/pharmacology MH - Wnt Signaling Pathway/*drug effects OTO - NOTNLM OT - Breast cancer OT - FH535 OT - MMP3 OT - Sphingosylphosphorylcholine OT - UK370106 OT - Wnt EDAT- 2016/05/25 06:00 MHDA- 2019/01/29 06:00 CRDT- 2016/05/25 06:00 PHST- 2016/01/28 00:00 [received] PHST- 2016/04/27 00:00 [revised] PHST- 2016/05/18 00:00 [accepted] PHST- 2016/05/25 06:00 [entrez] PHST- 2016/05/25 06:00 [pubmed] PHST- 2019/01/29 06:00 [medline] AID - S0925-4439(16)30118-1 [pii] AID - 10.1016/j.bbadis.2016.05.010 [doi] PST - ppublish SO - Biochim Biophys Acta. 2016 Sep;1862(9):1533-43. doi: 10.1016/j.bbadis.2016.05.010. Epub 2016 May 20.