TY  - JOUR
A1  - Boschert, Verena
A1  - Teusch, Jonas
A1  - Müller-Richter, Urs D. A.
A1  - Brands, Roman C.
A1  - Hartmann, Stefan
T1  - PKM2 modulation in head and neck squamous cell carcinoma
JF  - International Journal of Molecular Sciences
N2  - The enzyme pyruvate kinase M2 (PKM2) plays a major role in the switch of tumor cells from oxidative phosphorylation to aerobic glycolysis, one of the hallmarks of cancer. Different allosteric inhibitors or activators and several posttranslational modifications regulate its activity. Head and neck squamous cell carcinoma (HNSCC) is a common disease with a high rate of recurrence. To find out more about PKM2 and its modulation in HNSCC, we examined a panel of HNSCC cells using real-time cell metabolic analysis and Western blotting with an emphasis on phosphorylation variant Tyr105 and two reagents known to impair PKM2 activity. Our results show that in HNSCC, PKM2 is commonly phosphorylated at Tyrosine 105. Its levels depended on tyrosine kinase activity, emphasizing the importance of growth factors such as EGF (epidermal growth factor) on HNSCC metabolism. Furthermore, its correlation with the expression of CD44 indicates a role in cancer stemness. Cells generally reacted with higher glycolysis to PKM2 activator DASA-58 and lower glycolysis to PKM2 inhibitor Compound 3k, but some were more susceptible to activation and others to inhibition. Our findings emphasize the need to further investigate the role of PKM2 in HNSCC, as it could aid understanding and treatment of the disease.
KW  - HNSCC
KW  - head and neck cancer
KW  - cancer metabolism
KW  - glycolysis
KW  - PKM2
KW  - Warburg effect
KW  - CD44
KW  - Compound 3k
KW  - DASA-58
KW  - AMPK
KW  - TXNIP
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284458
SN  - 1422-0067
VL  - 23
IS  - 2
ER  -