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2015 ; 5
(ä): 16495
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NPM1 histone chaperone is upregulated in glioblastoma to promote cell survival
and maintain nucleolar shape
#MMPMID26559910
Holmberg Olausson K
; Elsir T
; Moazemi Goudarzi K
; Nistér M
; Lindström MS
Sci Rep
2015[Nov]; 5
(ä): 16495
PMID26559910
show ga
Glioblastoma (grade IV glioma) is the most common and aggressive adult brain
tumor. A better understanding of the biology of glioblastoma cells is crucial to
identify molecular targets stimulating cell death. NPM1 (nucleophosmin) is a
multifunctional chaperone that plays an important role in cancer development.
Herein, NPM1 was analyzed by immunohistochemistry in human astrocytic gliomas.
NPM1 was detected in all tumors but with a significantly higher staining
intensity in grade IV than in low grade tumors. Depletion of NPM1 had only modest
effects on the viability of U251MG, U1242MG, and U343MGa Cl2:6 glioma cells,
despite alterations in nucleolar morphology. Glioma cell cultures depleted of
NPM1 exposed to micromolar levels of actinomycin D were more prone to cell death
(apoptosis) compared to cultures retaining NPM1. We had previously found that
NPM1 binds to linker histone H1.5. Here we could show that silencing of H1.5
triggered glioma cell apoptosis as evidenced by a marked increase in both the
numbers of cleaved caspase-3(+) cells and in the amounts of cleaved PARP.
Enforced expression of NPM1 suppressed apoptosis in H1.5 depleted glioma cells.
Although our studies would suggest little effectiveness of targeting NPM1 alone
there could be potential using it as a combination treatment.