NPM1 histone chaperone is upregulated in glioblastoma to promote cell survival and maintain nucleolar shape

Olausson, KHKarolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden. (författare)

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.

Elsir, TUppsala universitet,Karolinska Institutet,Institutionen för neurovetenskap,Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden. (författare)
Goudarzi, KMKarolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden. (författare)
Nister, MKarolinska Institutet,Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden. (författare)
Lindstrom, MSKarolinska Institutet,Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden.;Karolinska Inst, Div Translat Med & Chem Biol, Dept Med Biochem & Biophys, Sci Life Lab, SE-17121 Stockholm, Sweden. (författare)
Karolinska InstitutetKarolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden. (creator_code:org_t)

Ingår i:Scientific reports: Springer Science and Business Media LLC5, s. 16495-2045-2322

Av författaren/redakt...: Olausson, KH; Elsir, T; Goudarzi, KM; Nister, M; Lindstrom, MS

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