DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ERBB signaling

Wen Chieh Liao, Chih Kai Liao, You Huan Tsai, To Jung Tseng, Li Ching Chuang, Chyn Tair Lan, Hung Ming Chang, Chiung Hui Liu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Remodeling of the extracellular matrix (ECM) in the tumor microenvironment promotes glioma progression. Chondroitin sulfate (CS) proteoglycans appear in the ECM and on the cell surface, and can be catalyzed by dermatan sulfate epimerase to form chondroitin sulfate/dermatan sulfate (CS/DS) hybrid chains. Dermatan sulfate epimerase 1 (DSE) is overexpressed in many types of cancer, and CS/DS chains mediate several growth factor signals. However, the role of DSE in gliomas has never been explored. In the present study, we determined the expression of DSE in gliomas by consulting a public database and conducting immunohistochemistry on a tissue array. Our investigation revealed that DSE was upregulated in gliomas compared with normal brain tissue. Furthermore, high DSE expression was associated with advanced tumor grade and poor survival. We found high DSE expression in several glioblastoma cell lines, and DSE expression directly mediated DS chain formation in glioblastoma cells. Knockdown of DSE suppressed the proliferation, migration, and invasion of glioblastoma cells. In contrast, overexpression of DSE in GL261 cells enhanced these malignant phenotypes and in vivo tumor growth. Interestingly, we found that DSE selectively regulated heparin-binding EGF-like growth factor (HB-EGF)-induced signaling in glioblastoma cells. Inhibiting epidermal growth factor receptor (EGFR) and ErbB2 with afatinib suppressed DSE-enhanced malignant phenotypes, establishing the critical role of the ErbB pathway in regulating the effects of DSE expression. This evidence indicates that upregulation of DSE in gliomas contributes to malignant behavior in cancer cells. We provide novel insight into the significance of DS chains in ErbB signaling and glioma pathogenesis.

Original languageEnglish
Article numbere0198364
JournalPLoS One
Volume13
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Racemases and Epimerases
Dermatan Sulfate
heparin
Glioma
growth factors
sulfates
Phenotype
phenotype
cells
Glioblastoma
chondroitin sulfate
Tumors
neoplasms
Heparin-binding EGF-like Growth Factor
extracellular matrix
Extracellular Matrix
Neoplasms
Cells
Tissue
Chondroitin Sulfate Proteoglycans

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Liao, W. C., Liao, C. K., Tsai, Y. H., Tseng, T. J., Chuang, L. C., Lan, C. T., ... Liu, C. H. (2018). DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ERBB signaling. PLoS One, 13(6), [e0198364]. https://doi.org/10.1371/journal.pone.0198364

DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ERBB signaling. / Liao, Wen Chieh; Liao, Chih Kai; Tsai, You Huan; Tseng, To Jung; Chuang, Li Ching; Lan, Chyn Tair; Chang, Hung Ming; Liu, Chiung Hui.

In: PLoS One, Vol. 13, No. 6, e0198364, 01.06.2018.

Research output: Contribution to journalArticle

Liao, WC, Liao, CK, Tsai, YH, Tseng, TJ, Chuang, LC, Lan, CT, Chang, HM & Liu, CH 2018, 'DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ERBB signaling', PLoS One, vol. 13, no. 6, e0198364. https://doi.org/10.1371/journal.pone.0198364
Liao WC, Liao CK, Tsai YH, Tseng TJ, Chuang LC, Lan CT et al. DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ERBB signaling. PLoS One. 2018 Jun 1;13(6). e0198364. https://doi.org/10.1371/journal.pone.0198364
Liao, Wen Chieh ; Liao, Chih Kai ; Tsai, You Huan ; Tseng, To Jung ; Chuang, Li Ching ; Lan, Chyn Tair ; Chang, Hung Ming ; Liu, Chiung Hui. / DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ERBB signaling. In: PLoS One. 2018 ; Vol. 13, No. 6.
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