Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Madreiter-Sokolowski, CT; Győrffy, B; Klec, C; Sokolowski, AA; Rost, R; Waldeck-Weiermair, M; Malli, R; Graier, WF.
UCP2 and PRMT1 are key prognostic markers for lung carcinoma patients.
Oncotarget. 2017; 8(46):80278-80285
Doi: 10.18632/oncotarget.20571
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- Führende Autor*innen der Med Uni Graz
- Graier Wolfgang
- Madreiter-Sokolowski Corina
- Co-Autor*innen der Med Uni Graz
- Klec Christiane
- Malli Roland
- Rost René
- Sokolowski Armin
- Waldeck-Weiermair Markus
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- Abstract:
- Cancer cells have developed unique strategies to meet their high energy demand. Therefore, they have established a setting of Ca2+-triggered high mitochondrial activity. But mitochondrial Ca2+ uptake has to be strictly controlled to avoid mitochondrial Ca2+ overload that would cause apoptotic cell death. Methylation by protein arginine methyl transferase 1 (PRMT1) desensitizes the mitochondrial Ca2+ uptake machinery and reduces mitochondrial Ca2+ accumulation in cancer cells. In case of PRMT1-driven methylation, proper mitochondrial Ca2+ uptake is reestablished by increased activity of uncoupling protein 2 (UCP2), pointing to an importance of these proteins for cancer cell survival and activity. Accordingly, in this study we investigated the impact of UCP2 and PRMT1 on the fate of human lung cancer cells (A549, Calu-3 and H1299) as well as on patients suffering from lung carcinoma. We show that combined overexpression of UCP2 and PRMT1 significantly enhances viability, proliferation as well as mitochondrial respiration. In line with these findings, the overall survival probability of lung carcinoma patients with high mRNA expression levels of UCP2 and PRMT1 is strongly reduced. Furthermore, analysis via The Cancer Genome Atlas (TCGA) reveals upregulation of both proteins, UCP2 and PRMT1, as common feature of various cancer types. These findings suggest that proper mitochondrial Ca2+ uptake is essential for devastating tumor growth, and highlight the importance of a tightly controlled mitochondrial Ca2+ uptake to ensure proper ATP biosynthesis while avoiding dangerous mitochondrial Ca2+ overload. By that, the study unveils proteins of the mitochondrial Ca2+ uptake as potential targets for cancer treatment.
- Find related publications in this database (Keywords)
- lung cancer cell proliferation
- mitochondria
- Ca2+ controls respiration
- protein arginine methyltransferase 1
- uncoupling protein 2