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Role for the ATPase inhibitory factor 1 in the environmental carcinogen-induced Warburg phenotype.
- Source :
-
Scientific reports [Sci Rep] 2017 Mar 15; Vol. 7 (1), pp. 195. Date of Electronic Publication: 2017 Mar 15. - Publication Year :
- 2017
-
Abstract
- Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accepted but little is known about the underlying intracellular mechanisms. Among the environmental pollutants humans are commonly exposed to, benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons (PAHs), is a well-known human carcinogen. Besides apoptotic signals, B[a]P can also induce survival signals in liver cells, both likely involved in cancer promotion. Our previous works showed that B[a]P elicited a Warburg-like effect, thus favoring cell survival. The present study aimed at further elucidating the molecular mechanisms involved in the B[a]P-induced metabolic reprogramming, by testing the possible involvement of IF1. We presently demonstrate, both in vitro and in vivo, that PAHs, especially B[a]P, strongly increase IF1 expression. Such an increase, which might rely on β2-adrenergic receptor activation, notably participates to the B[a]P-induced glycolytic shift and cell survival in liver cells. By identifying IF1 as a target of PAHs, this study provides new insights about how environmental factors may contribute to related carcinogenesis.
- Subjects :
- Animals
Apoptosis
Benzo(a)pyrene toxicity
Carcinoma, Hepatocellular chemically induced
Carcinoma, Hepatocellular metabolism
Cell Line
Cell Survival
Disease Progression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic drug effects
Humans
Liver Neoplasms chemically induced
Liver Neoplasms metabolism
Neoplasms, Experimental
Proteins metabolism
Rats
Receptors, Adrenergic, beta-2 genetics
Signal Transduction drug effects
Up-Regulation
ATPase Inhibitory Protein
Carcinogens, Environmental toxicity
Carcinoma, Hepatocellular genetics
Glycolysis
Liver Neoplasms genetics
Polycyclic Aromatic Hydrocarbons toxicity
Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28298645
- Full Text :
- https://doi.org/10.1038/s41598-017-00269-7