α2,3-sialyltransferase type I regulates migration and peritoneal dissemination of ovarian cancer cells

Abstract

Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecologic cancers due to advanced stage presentation, peritoneal dissemination, and refractory ascites at diagnosis. We investigated the role of α2,3-sialyltransferase type I (ST3GalI) by analyzing human ovarian cancer datasets and human EOC tissue arrays. We found that high expression of ST3GalI was associated with advanced stage EOC. Transwell migration and cell invasion assays showed that high ST3GalI expression enhanced migration of EOC cells. We also observed that there was a linear relation between ST3GalI expression and epidermal growth factor receptor (EGFR) signaling in EOC patients, and that high ST3GalI expression blocked the effect of EGFR inhibitors. Co-Immunoprecipitation experiments demonstrated that ST3GalI and EGFR were present in the same protein complex. Inhibition of ST3GalI using a competitive inhibitor, Soyasaponin I (SsaI), inhibited tumor cell migration and dissemination in the in vivo mouse model with transplanted MOSEC cells. Further, SsaI synergistically enhanced the anti-tumor effects of EGFR inhibitor on EOC cells. Our study demonstrates that ST3GalI regulates ovarian cancer cell migration and peritoneal dissemination via EGFR signaling. This suggests α2,3-linked sialylation inhibitors in combination with EGFR inhibitors could be effective agents for the treatment of EOC.

Sialyltransferase ST3GAL1 promotes cell migration, invasion, and TGF-β1-induced EMT and confers paclitaxel resistance in ovarian cancer

“…It has been suggested that the increased expression of ST3GAL1 in ovarian serous carcinoma may contribute directly to increased alpha2,3-linked sialylation 36 . Recent research supports our finding that ST3GAL1 expression is increased in serous ovarian cancer and demonstrates that ST3GAL1 may regulate ovarian cancer cell migration and peritoneal dissemination via epidermal growth factor receptor (EGFR) signaling 37 . The EGFR signaling pathway is known to be overexpressed and associated with poor prognosis in more than 70% of ovarian cancer patients 38 .…”

Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

“…In prostate cancer, overexpression of galectin-4 relates to malignancy because it binds on the O -linked carbohydrate antigen T ( Table 1 ), activating EGFR/ERBB2 signaling [ 124 ]. On the other hand, a positive relationship among the expression of ST3GAL1, the enzyme thatconverts the T antigen in sialyl-T antigen ( Table 1 ), EGFR signaling and malignancy has also been documented [ 71 ].…”

Increase of MAL-II Binding Alpha2,3-Sialylated Glycan Is Associated with 5-FU Resistance and Short Survival of Cholangiocarcinoma Patients

“…The results showed that both MAL-SG (α2,3-sialylated glycan) and SNA-SG (α2,6-sialylated glycan) expression were higher in CCA compared to NBD and HP/DP, suggesting the possible association between the increase of sialylation and CCA development. Although the mechanisms underlying the increase of sialylation in CCA were not yet clearly defined, it is possible to be triggered by the increase of sialic acid synthesis or sialyltransferases and/or the decrease of sialidases, as was shown previously in other cancers [33,36,37].…”

“…An association between the increased sialylation and cancer progression has been demonstrated in various cancers as it plays important roles in metastasis, immune evasion, radioresistance, and chemoresistance [21,[37][38][39]. Elevation of α2,3-sialylated-glycans via increase of α2,3-sialyltransferase was associated with metastasis of gastric cancer [33] and the advanced stage of ovarian cancer [31].…”