Publications

Authors:

Belisario, Dimas Carolina; Kopecka, Joanna; Pasino, Martina; Akman, Muhlis; De Smaele, Enrico; Donadelli, Massimo; Riganti, Chiara

Title:

Hypoxia dictates metabolic rewiring of tumors: implications for chemoresistance

Year:

2020

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

CELLS

ISSN of journal:

2073-4409

N° Volume:

9

Number or Folder:

2598

Page numbers:

1-29

Keyword:

hypoxia; cancer; chemoresistance; metabolic reprogramming

Short description of contents:

Hypoxia is a condition commonly observed in the core of solid tumors. The hypoxia-inducible factors (HIF) act as hypoxia sensors that orchestrate a coordinated response increasing the pro-survival and pro-invasive phenotype of cancer cells, and determine a broad metabolic rewiring. These events favor tumor progression and chemoresistance. The increase in glucose and amino acid uptake, glycolytic flux, and lactate production; the alterations in glutamine metabolism, tricarboxylic acid cycle, and oxidative phosphorylation; the high levels of mitochondrial reactive oxygen species; the modulation of both fatty acid synthesis and oxidation are hallmarks of the metabolic rewiring induced by hypoxia. This review discusses how metabolic-dependent factors (e.g., increased acidification of tumor microenvironment coupled with intracellular alkalinization, and reduced mitochondrial metabolism), and metabolic-independent factors (e.g., increased expression of drug efflux transporters, stemness maintenance, and epithelial-mesenchymal transition) cooperate in determining chemoresistance in hypoxia. Specific metabolic modifiers, however, can reverse the metabolic phenotype of hypoxic tumor areas that are more chemoresistant into the phenotype typical of chemosensitive cells. We propose these metabolic modifiers, able to reverse the hypoxia-induced metabolic rewiring, as potential chemosensitizer agents against hypoxic and refractory tumor cells.

Web page:

https://doi.org/10.3390/cells9122598

Product ID:

118256

Handle IRIS:

11562/1031987

Last Modified:

November 17, 2022

Bibliographic citation:

Belisario, Dimas Carolina; Kopecka, Joanna; Pasino, Martina; Akman, Muhlis; De Smaele, Enrico; Donadelli, Massimo; Riganti, Chiara, Hypoxia dictates metabolic rewiring of tumors: implications for chemoresistance «CELLS» , vol. 9 , n. 2598 , 2020 , pp. 1-29

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