The src-family kinase feline gardner-rasheed is implicated in chronic lymphocytic leukemia cellular metabolic regulation

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Date
2017
Authors
Ciapala, Alexandra Christine Caces
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Abstract
Alterations intrinsic to Chronic Lymphocytic Leukemia (CLL) cells affect many signaling pathways, including those relating to proliferation and evasion of apoptosis. Interactions with the microenvironment further alter survival, proliferative, and metabolic signaling of CLL cells. Feline Gardner-Rasheed (Fgr) is a Src-family kinase implicated in B cell receptor signaling and metabolism. Its expression is variable and its function is unknown in CLL cells. The ability of CLL cells to regulate their metabolism in response to energy demand is key to their ability to sustain proliferation and survive cellular stress. We hypothesize that Fgr expression correlates with clinical parameters, and contributes to signaling that enhances cell survival and metabolic adaptation to energy demand. In a transiently-transfected BJAB cell line, we found that Fgr over expression increased glycolysis and mitochondrial respiratory capacity in BJAB cells. This correlated with the ability of Fgr to activate complex II in the mitochondria. Furthermore, Fgr expression provided cell survival signaling following treatment with metabolic toxins. Finally, we found that Fgr expression correlates positively with favourable prognosis markers in CLL cells. This suggests that Fgr regulates metabolism and cell survival in CLL cells.
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CLL, Chronic lymphocytic leukemia, Leukemia, Leukaemia, B-cell, Cancer, Fgr, Feline gardner-rasheed, Metabolism, Metabolic regulation, Succinate dehydrogenase, Mitochondria, Kinase, Tyrosine kinase
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