Deregulated expression and activity of Farnesyl Diphosphate Synthase (FDPS) in Glioblastoma

Scientific Reports
Mario AbateElena Ciaglia

Abstract

Glioblastoma (GBM), the most aggressive brain cancer, is highly dependent on the mevalonate (MVA) pathway for the synthesis of lipid moieties critical for cell proliferation but the function and regulation of key intermediate enzymes like farnesyl-diphosphate synthase (FDPS), up to now, remained unknown. A deregulated expression and activity of FDPS was the central research idea of the present study. FDPS mRNA, protein and enzyme activity were analyzed in a cohort of stage III-IV glioma patients (N = 49) and primary derived cells. FDPS silencing helped to clarify its function in the maintenance of malignant phenotype. Interestingly, compared to tumor-free peripheral (TFB) brain and normal human astrocytes (NHA), FDPS protein expression and enzyme activity were detected at high degree in tumor mass where a correlation with canonical oncogenic signaling pathways such as STAT3, ERK and AKT was also documented. Further, FDPS knockdown in U87 and GBM primary cells but not in NHA, enhanced apoptosis. With the effort to develop a more refined map of the connectivity between signal transduction pathways and metabolic networks in cancer FDPS as a new candidate metabolic oncogene in glioblastoma, might suggest to further target MVA pathw...Continue Reading

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Citations

Feb 2, 2018·Journal of Leukocyte Biology·Antonietta SantoroElena Ciaglia
Jan 30, 2019·Cancers·Fahim AhmadJayne M Stommel
Nov 21, 2019·Journal of Cellular and Molecular Medicine·Shupei WeiTao Chen
May 15, 2018·International Journal of Molecular Sciences·Jure TicaAthanasios Didangelos
Jan 22, 2019·Frontiers in Pharmacology·Huanbiao MoHoda Yeganehjoo
May 28, 2020·International Journal of Molecular Sciences·Mario AbateRosanna Martinelli
Oct 16, 2018·Frontiers in Oncology·Gabriela Galicia-Vázquez, Raquel Aloyz
Jul 10, 2019·Natural Product Research·Boris PejinVesna Kojic
Jul 31, 2020·BMC Cancer·Andy GöbelTilman D Rachner
Oct 20, 2018·Experimental & Molecular Medicine·Hee Yeon KimHyonchol Jang
Nov 27, 2020·Cell·Francesca PetraliaUNKNOWN Clinical Proteomic Tumor Analysis Consortium
Feb 7, 2021·Nature Communications·Yue-Yue LiuAi-Jun Miao
Feb 3, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Andy GöbelTilman D Rachner
Mar 7, 2021·International Journal of Molecular Sciences·Mario AbateRosanna Martinelli

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Methods Mentioned

BETA
GTPase
xenograft
transfection
reverse transcription-PCR
X-ray
PCR

Software Mentioned

GraphPad
FDPS
GraphPad prism
ModFit LT
CellQuest Pro
Quantity One

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