1. Pyruvate Kinase Differentially Alters Metabolic Signatures during Head and Neck Carcinogenesis.
- Author
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Huang, Pei-Chun, Chang, Ching-Wen, Lin, Yu-Cheng, Chen, Chang-Yi, Chen, Tsai-Ying, Chuang, Lu-Te, Liu, Chung-Ji, Huang, Chien-Ling, and Li, Wan-Chun
- Subjects
PYRUVATE kinase ,PROTEIN kinase B ,ONCOGENIC proteins ,NECK ,COMMODITY exchanges ,GENE expression - Abstract
During glycolysis, the muscle isoform of pyruvate kinase PKM2 produces ATP in exchange for dephosphorylation of phosphoenolpyruvate (PEP) into pyruvate. PKM2 has been considered as a tumor-promoting factor in most cancers, whereas the regulatory role of PKM2 during head and neck carcinogenesis remained to be delineated. PKM2 mRNA and protein expression was examined in head and neck tumorous specimens. The role of PKM2 in controlling cellular malignancy was determined in shRNA-mediated PKM2-deficient head and neck squamous cell carcinoma (HNSC) cells. In agreement with the results in other cancers, PKM2 expression is enriched in both mouse and human HNSC tissues. Nevertheless, PKM2 mRNA expression reversely correlated with tumor stage, and greater recurrence-free survival rates are evident in the PKM2
high HNSC population, arguing that PKM2 may be tumor-suppressive. Multifaceted analyses showed a greater in vivo xenografic tumor growth and an enhanced cisplatin resistance in response to PKM2 loss, whereas PKM2 silencing led to reduced cell motility. At the molecular level, metabolic shifts towards mitochondrial metabolism and activation of oncogenic Protein kinase B (PKB/Akt) and extracellular signal-regulated kinase (ERK) signals were detected in PKM2-silencing HNSC cells. In sum, our findings demonstrated that PKM2 differentially modulated head and neck tumorigenicity via metabolic reprogramming. [ABSTRACT FROM AUTHOR]- Published
- 2023
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