The Ig superfamily protein PTGFRN coordinates survival signaling in glioblastoma multiforme.
Animals
Apoptosis
Biomarkers, Tumor
/ genetics
Brain Neoplasms
/ genetics
Cell Proliferation
DNA Damage
DNA Repair
Gene Expression Regulation, Neoplastic
Glioblastoma
/ genetics
Humans
Mice
Mice, Nude
Neoplasm Proteins
/ genetics
Phosphatidylinositol 3-Kinases
/ genetics
Phosphorylation
Prognosis
Proto-Oncogene Proteins c-akt
/ genetics
Radiation Tolerance
Radiation, Ionizing
Signal Transduction
Survival Rate
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
AKT
Glioblastoma multiforme
PI3K p110β
PTGFRN
Radiation
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
10 10 2019
10 10 2019
Historique:
received:
05
04
2019
revised:
23
07
2019
accepted:
27
07
2019
pubmed:
5
8
2019
medline:
22
5
2020
entrez:
5
8
2019
Statut:
ppublish
Résumé
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with a median survival of approximately 14 months. Despite aggressive treatment of surgical resection, chemotherapy and radiation therapy, only 3-5% of GBM patients survive more than 3 years. Contributing to this poor therapeutic response, it is believed that GBM contains both intrinsic and acquired mechanisms of resistance, including resistance to radiation therapy. In order to define novel mediators of radiation resistance, we conducted a functional knockdown screen, and identified the immunoglobulin superfamily protein, PTGFRN. In GBM, PTGFRN is found to be overexpressed and to correlate with poor survival. Reducing PTGFRN expression radiosensitizes GBM cells and potently decreases the rate of cell proliferation and tumor growth. Further, PTGFRN inhibition results in significant reduction of PI3K p110β and phosphorylated AKT, due to instability of p110β. Additionally, PTGFRN inhibition decreases nuclear p110β leading to decreased DNA damage sensing and DNA damage repair. Therefore overexpression of PTGFRN in glioblastoma promotes AKT-driven survival signaling and tumor growth, as well as increased DNA repair signaling. These findings suggest PTGFRN is a potential signaling hub for aggressiveness in GBM.
Identifiants
pubmed: 31377205
pii: S0304-3835(19)30414-8
doi: 10.1016/j.canlet.2019.07.018
pmc: PMC6705426
mid: NIHMS1536850
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Neoplasm Proteins
0
PTGFRN protein, human
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
33-42Subventions
Organisme : NCI NIH HHS
ID : R01 CA187053
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA187780
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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