Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to, WNT activation
- Authors
- Kim, Hyun Ji; Kang, Gyeoung Jin; Kim, Eun Ji; Park, Mi Kyung; Byun, Hyun Jung; Nam, Seungyoon; Lee, Ho; Lee, Chang Hoon
- Issue Date
- Sep-2016
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Sphingosylphosphorylcholine; MMP3; UK370106; Wnt; FH535; Breast cancer
- Citation
- BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v.1862, no.9, pp.1533 - 1543
- Journal Title
- BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
- Volume
- 1862
- Number
- 9
- Start Page
- 1533
- End Page
- 1543
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/7949
- DOI
- 10.1016/j.bbadis.2016.05.010
- ISSN
- 0925-4439
- Abstract
- 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 Icinase (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 ERIC leading to Wnt activation. (C) 2016 Elsevier B.V. All rights reserved.
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