The role of glycolysis in tumorigenesis: from biological aspects to therapeutic opportunities
Yükleniyor...
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier inc.
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Glycolytic metabolism generates energy and intermediates for biomass production. Tumor-associated glycolysis is upregulated compared to normal tissues in response to tumor cell-autonomous or non-autonomous stimuli. The consequences of this upregulation are twofold. First, the metabolic effects of glycolysis become predominant over those mediated by oxidative metabolism. Second, overexpressed components of the glycolytic pathway (i.e. enzymes or metabolites) acquire new functions unrelated to their metabolic effects and which are referred to as "moonlighting" functions. These functions include induction of mutations and other tumor-initiating events, effects on cancer stem cells, induction of increased expression and/or activity of oncoproteins, epigenetic and transcriptional modifications, bypassing of senescence and induction of proliferation, promotion of DNA damage repair and prevention of DNA damage, antiapoptotic effects, inhibition of drug influx or increase of drug efflux. Upregulated metabolic functions and acquisition of new, non-metabolic functions lead to biological effects that support tumorigenesis: promotion of tumor initiation, stimulation of tumor cell proliferation and primary tumor growth, induction of epithelial-mesenchymal transition, autophagy and metastasis, immunosuppressive effects, induction of drug resistance and effects on tumor accessory cells. These effects have negative consequences on the prognosis of tumor patients. On these grounds, it does not come to surprise that tumor-associated glycolysis has become a target of interest in antitumor drug discovery. So far, however, clinical results with glycolysis inhibitors have fallen short of expectations. In this review we propose approaches that may allow to bypass some of the difficulties that have been encountered so far with the therapeutic use of glycolysis inhibitors.
Açıklama
Anahtar Kelimeler
Anticancer Therapies, Cancer Stem Cells, Glycolysis, Metabolic Reprogramming, Tumorigenesis
Kaynak
Neoplasia
WoS Q DeÄŸeri
Q1
Scopus Q DeÄŸeri
Q2
Cilt
58
Sayı
Künye
Cordani, M., Michetti, F., Zarrabi, A., Zarepour, A., Rumio, C., Strippoli, R., & Marcucci, F. (2024). The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities. Neoplasia, 58, 101076.
