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Abstract
In this study we aimed at studying the tumor aggressiveness and differentiation potential of Ramos Burkitt’s lymphoma cells upon mitogenic stimulation in light of a novel regulator of immune cell metabolism and activation, ADPGK. We have identified the role of ADPGK in regulation of aerobic glycolysis in Burkitt’s Lymphoma cells and shown that its knock-out leads to reduced tumor aggressiveness, as measured in-vitro via co-culture, migration experiments and metabolic profile, and in-vivo Zebrafish. We found significantly reduced MYC transcription in ADPGK knock-out Burkitt’s lymphoma cells and importantly, several folds reduction in accumulated random mutations in translocated MYC in these cells. We additionally observed a stalled pathway to differentiation of ADPGK knock out B-cells into plasma cells upon stimulation by mitogenic signals. Overall, the study provided the first insights into the role of a novel ER resident protein acting as a regulator of two complementary phenomenon, cell-differentiation and cancer aggressiveness, and thereby opens up new possibilities of therapeutic interventions for hematopoietic malignancies.
Dokumententyp: | Dissertation |
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Erstgutachter: | Sauer, PD Dr. Sven |
Ort der Veröffentlichung: | Heidelberg, Germany |
Tag der Prüfung: | 21 November 2018 |
Erstellungsdatum: | 21 Dez. 2018 09:33 |
Erscheinungsjahr: | 2018 |
Institute/Einrichtungen: | Fakultät für Biowissenschaften > Dekanat der Fakultät für Biowissenschaften |
DDC-Sachgruppe: | 500 Naturwissenschaften und Mathematik
570 Biowissenschaften, Biologie |