Sialylation of FGFR1 by ST6Gal‑I overexpression contributes to ovarian cancer cell migration and chemoresistance.

Abstract:

:Fibroblast growth factor receptors (FGFRs) have been implicated in the malignant transformation and chemoresistance of epithelial ovarian cancer; however, the underlying molecular mechanisms are poorly understood. Increased sialyltransferase activity that enhances protein sialylation is an important post‑translational process promoting cancer progression and malignancy. In the present study, α2,6‑sialyltransferase (ST6Gal‑I) overexpression or knockdown cell lines were developed, and FGFR1 was examined to understand the effect of sialylation on migration and drug resistance, and the underlying mechanisms. It was identified that cells with ST6Gal‑I overexpression had increased cell viability and migratory ability upon serum deprivation. Moreover, ST6Gal‑I overexpression cells had strong resistance to paclitaxel, as demonstrated by low growth inhibition rate and cell apoptosis level. A mechanistic study showed that ST6Gal‑I overexpression induced high α2,6‑sialylation of FGFR1 and increased the expression of phospho‑ERK1/2 and phospho‑focal adhesion kinase. Further study demonstrated that the FGFR1 inhibitor PD173047 reduced cell viability and induced apoptosis; however, ST6Gal‑I overexpression decreased the anticancer effect of PD173047. In addition, ST6Gal‑I overexpression attenuated the effect of Adriamycin on cancer cells. Collectively, these results suggested that FGFR1 sialylation plays an important role in cell migration and drug chemoresistance in ovarian cancer cells.

journal_name

Mol Med Rep

authors

Ou L,He X,Liu N,Song Y,Li J,Gao L,Huang X,Deng Z,Wang X,Lin S

doi

10.3892/mmr.2020.10951

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

1449-1460

issue

3

eissn

1791-2997

issn

1791-3004

journal_volume

21

pub_type

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