Biomol Ther.  2017 Nov;25(6):625-633. 10.4062/biomolther.2016.228.

Sphingosylphosphorylcholine Induces Thrombospondin-1 Secretion in MCF10A Cells via ERK2

• Kang JH
• Kim HJ
• Park MK
• Lee CH

• KMID: 2395812
• DOI: http://doi.org/10.4062/biomolther.2016.228

Abstract

Sphingosylphosphorylcholine (SPC) is one of the bioactive phospholipids that has many cellular functions such as cell migration, adhesion, proliferation, angiogenesis, and Ca²âº signaling. Recent studies have reported that SPC induces invasion of breast cancer cells via matrix metalloproteinase-3 (MMP-3) secretion leading to WNT activation. Thrombospondin-1 (TSP-1) is a matricellular and calcium-binding protein that binds to a wide variety of integrin and non-integrin cell surface receptors. It regulates cell proliferation, migration, and apoptosis in inflammation, angiogenesis and neoplasia. TSP-1 promotes aggressive phenotype via epithelial mesenchymal transition (EMT). The relationship between SPC and TSP-1 is unclear. We found SPC induced EMT leading to mesenchymal morphology, decrease of E-cadherin expression and increases of N-cadherin and vimentin. SPC induced secretion of thrombospondin-1 (TSP-1) during SPC-induced EMT of various breast cancer cells. Gene silencing of TSP-1 suppressed SPC-induced EMT as well as migration and invasion of MCF10A cells. An extracellular signal-regulated kinase inhibitor, PD98059, significantly suppressed the secretion of TSP-1, expressions of N-cadherin and vimentin, and decrease of E-cadherin in MCF10A cells. ERK2 siRNA suppressed TSP-1 secretion and EMT. From online PROGgene V2, relapse free survival is low in patients having high TSP-1 expressed breast cancer. Taken together, we found that SPC induced EMT and TSP-1 secretion via ERK2 signaling pathway. These results suggests that SPC-induced TSP-1 might be a new target for suppression of metastasis of breast cancer cells.

Keyword

Sphingosylphosphorylcholine; Thrombospondin-1; Epithelial mesenchymal transition; ERK2

MeSH Terms

Apoptosis
Breast Neoplasms
Cadherins
Cell Movement
Cell Proliferation
Epithelial-Mesenchymal Transition
Gene Silencing
Humans
Inflammation
Neoplasm Metastasis
Phenotype
Phospholipids
Phosphotransferases
Receptors, Cell Surface
Recurrence
RNA, Small Interfering
Thrombospondin 1
Vimentin
Cadherins
Phospholipids
Phosphotransferases
RNA, Small Interfering
Receptors, Cell Surface
Thrombospondin 1
Vimentin