Structural alteration of cell surface heparan sulfate through the stimulation of the signaling pathway for heparan sulfate 6-O-sulfotransferase-1 in mouse fibroblast cells

Abstract

Heparan sulfate (HS) is a randomly sulfated polysaccharide that is present on the cell surface and in the extracellular matrix. The sulfated structures of HS were synthesized by multiple HS sulfotransferases, thereby regulating various activities such as growth factor signaling, cell differentiation, and tumor metastasis. Therefore, if the sulfated structures of HS could be artificially controlled, those manipulations would help to understand the various functions depending on HS. However, little knowledge is currently available to realize the mechanisms controlling the expression of such enzymes. In this study, we found that the ratio of 6-O-sulfated disaccharides increased at 3 h after adrenaline stimulation in mouse fibroblast cells. Furthermore, adrenaline-induced up-regulation of HS 6-O-sulfotransferase-1 (6-OST-1) was controlled by Src-ERK1/2 signaling pathway. Finally, inhibiting the signaling pathways for 6-OST-1 intentionally suppressed the adrenaline-induced structural alteration of HS. These observations provide fundamental insights into the understanding of structural alterations in HS by extracellular cues.

Stress-induced epinephrine promotes hepatocellular carcinoma progression via the USP10-PLAGL2 signaling loop

“…Epinephrine promotes the synthesis of heparan sulfate by upregulating the expression of 6-O-sulfotransferase-1 (6-OST-1) through the Src-ERK1/2 signaling pathway. Furthermore, epinephrine increases the activity of murine fibroblasts, thus promoting tumor metastasis 36 . However, recent evidence shows that exercise-induced epinephrine could suppress tumor growth 37 .…”