RT Journal Article
SR Electronic
T1 Desert Hedgehog Down-regulation Mediates Inhibition of Proliferation by γ-Glutamylcyclotransferase Knockdown in Murine Glioblastoma Stem Cells
JF Cancer Genomics - Proteomics
JO Cancer Genomics Proteomics
FD International Institute of Anticancer Research
SP 474
OP 484
DO 10.21873/cgp.20465
VO 21
IS 5
A1 MORI, MASAYA
A1 II, HIROMI
A1 FUJITA, MITSUGU
A1 NOSE, KOZUE
A1 SHIMADA, AYAKO
A1 SHIRAKI, RISA
A1 SONE, YUHI
A1 MOYAMA, CHIAMI
A1 TANIGUCHI, KEIKO
A1 NAKATA, SUSUMU
YR 2024
UL http://cgp.iiarjournals.org/content/21/5/474.abstract
AB Background/Aim: Glioblastoma is the most frequent type of adult-onset malignant brain tumor and has a very poor prognosis. Glioblastoma stem cells have been shown to be one of the mechanisms by which glioblastoma acquires therapy resistance. Therefore, there is a need to establish novel therapeutic strategies useful for inhibiting this cell population. γ-Glutamylcyclotransferase (GGCT) is an enzyme involved in the synthesis and metabolism of glutathione, which is highly expressed in a wide range of cancer types, including glioblastoma, and inhibition of its expression has been reported to have antitumor effects on various cancer types. The aim of this study was to clarify the function of GGCT in glioblastoma stem cells. Materials and Methods: We searched for pathways affected by GGCT overexpression in mouse embryonic fibroblasts NIH-3T3 by comprehensive gene expression analysis. Knockdown of GGCT and overexpression of desert hedgehog (DHH), a representative ligand of the pathway, were performed in glioblastoma stem cells derived from a mouse glioblastoma model. Results: GGCT overexpression activated the hedgehog pathway. Knockdown of GGCT inhibited proliferation of glioblastoma stem cells and reduced expression of DHH and the downstream target GLI family zinc finger 1 (GLI1). DHH overexpression significantly restored the growth-suppressive effect of GGCT knockdown. Conclusion: High GGCT expression is important for expression of DHH and activation of the hedgehog pathway, which is required to maintain glioblastoma stem cell proliferation. Therefore, inhibition of GGCT function may be useful in suppressing stemness of glioblastoma stem cells accompanied by activation of the hedgehog pathway.