TY  - JOUR
A1  - Boschert, Verena
A1  - Klenk, Nicola
A1  - Abt, Alexander
A1  - Raman, Sudha Janaki
A1  - Fischer, Markus
A1  - Brands, Roman C.
A1  - Seher, Axel
A1  - Linz, Christian
A1  - Müller-Richter, Urs D. A.
A1  - Bischler, Thorsten
A1  - Hartmann, Stefan
T1  - The influence of Met receptor level on HGF-induced glycolytic reprogramming in head and neck squamous cell carcinoma
JF  - International Journal of Molecular Sciences
N2  - Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Met\(^{high}\)-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.
KW  - HNSCC
KW  - head and neck cancer
KW  - HGF
KW  - Met
KW  - cancer metabolism
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235995
SN  - 1422-0067
VL  - 21
IS  - 2
ER  - 
TY  - JOUR
A1  - De Lira, Maria Nathalia
A1  - Raman, Sudha Janaki
A1  - Schulze, Almut
A1  - Schneider-Schaulies, Sibylle
A1  - Avota, Elita
T1  - Neutral Sphingomyelinase-2 (NSM 2) Controls T Cell Metabolic Homeostasis and Reprogramming During Activation
JF  - Frontiers in Molecular Biosciences
N2  - Neutral sphingomyelinase-2 (NSM2) is a member of a superfamily of enzymes responsible for conversion of sphingomyelin into phosphocholine and ceramide at the cytosolic leaflet of the plasma membrane. Upon specific ablation of NSM2, T cells proved to be hyper-responsive to CD3/CD28 co-stimulation, indicating that the enzyme acts to dampen early overshooting activation of these cells. It remained unclear whether hyper-reactivity of NSM2-deficient T cells is supported by a deregulated metabolic activity in these cells. Here, we demonstrate that ablation of NSM2 activity affects metabolism of the quiescent CD4\(^+\) T cells which accumulate ATP in mitochondria and increase basal glycolytic activity. This supports enhanced production of total ATP and metabolic switch early after TCR/CD28 stimulation. Most interestingly, increased metabolic activity in resting NSM2-deficient T cells does not support sustained response upon stimulation. While elevated under steady-state conditions in NSM2-deficient CD4\(^+\) T cells, the mTORC1 pathway regulating mitochondria size, oxidative phosphorylation, and ATP production is impaired after 24 h of stimulation. Taken together, the absence of NSM2 promotes a hyperactive metabolic state in unstimulated CD4\(^+\) T cells yet fails to support sustained T cell responses upon antigenic stimulation.
KW  - neutral sphingomyelinase-2
KW  - T cell receptor
KW  - Seahorse XF
KW  - oxidative phosphorylation
KW  - ATP-adenosine triphosphate
KW  - Mitochondria
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211311
SN  - 2296-889X
VL  - 7
ER  -