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Review
. 2021 Oct 31;13(21):5484.
doi: 10.3390/cancers13215484.

Lipid Catabolism and ROS in Cancer: A Bidirectional Liaison

Serena Castelli  1 , Pamela De Falco  1 , Fabio Ciccarone  2 , Enrico Desideri  1 , Maria Rosa Ciriolo  1   3
Affiliations
Review

Lipid Catabolism and ROS in Cancer: A Bidirectional Liaison

Serena Castelli et al. Cancers (Basel). .

Abstract

Although cancer cell metabolism was mainly considered to rely on glycolysis, with the concomitant impairment of mitochondrial metabolism, it has recently been demonstrated that several tumor types are sustained by oxidative phosphorylation (OXPHOS). In this context, endogenous fatty acids (FAs) deriving from lipolysis or lipophagy are oxidised into the mitochondrion, and are used as a source of energy through OXPHOS. Because the electron transport chain is the main source of ROS, cancer cells relying on fatty acid oxidation (FAO) need to be equipped with antioxidant systems that maintain the ROS levels under the death threshold. In those conditions, ROS can act as second messengers, favouring proliferation and survival. Herein, we highlight the different responses that tumor cells adopt when lipid catabolism is augmented, taking into account the different ROS fates. Many papers have demonstrated that the pro- or anti-tumoral roles of endogenous FA usage are hugely dependent on the tumor type, and on the capacity of cancer cells to maintain redox homeostasis. In light of this, clinical studies have taken advantage of the boosting of lipid catabolism to increase the efficacy of tumor therapy, whereas, in other contexts, antioxidant compounds are useful to reduce the pro-survival effects of ROS deriving from FAO.

Keywords: fatty acid oxidation; lipid catabolism; mitochondrial metabolism; reactive oxygen species.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Role of FAs deriving from lipolysis and lipophagy. Besides the energetic role that FAs play when oxidised into mitochondria, they are useful in membrane building block biosynthesis. This function regulates the fluidity of the plasma membrane, which increases during the metastatic process. Moreover, FAs can act as second messengers, activating transcriptional factors and transducing the signal into the nucleus.
Figure 2
Figure 2
The balance between ROS production and elimination contributes to the regulation of tumor cell proliferation. FAO is responsible for mitochondrial ROS production, which in turn is buffered by intracellular antioxidants. Downstream of FAO, the ROS are low in tumor cells equipped with prominent antioxidant systems, whereas the ROS are high if not properly buffered. In this case, ROS are able to activate redox-sensitive transcription factors (e.g., HIF1α, AMPK, PPARγ), inducing cell proliferation. Instead, more efficient antioxidant systems allow FAs to play a signaling role, activating selective transcription factors (e.g., PPARα, p53), reducing cell proliferation.
Figure 3
Figure 3
A schematic representation of the mechanism of action exploited by the different compounds mentioned.
See this image and copyright information in PMC

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References

    1. Oliveira G.L., Coelho A.R., Marques R., Oliveira P.J. Cancer Cell Metabolism: Rewiring the Mitochondrial Hub. Biochim. Biophys. Acta Mol. Basis Dis. 2021;1867:166016. doi: 10.1016/j.bbadis.2020.166016. - DOI - PubMed
    1. Al Tameemi W., Dale T.P., Al-Jumaily R.M.K., Forsyth N.R. Hypoxia-Modified Cancer Cell Metabolism. Front. Cell Dev. Biol. 2019;7:4. doi: 10.3389/fcell.2019.00004. - DOI - PMC - PubMed
    1. Vasan K., Werner M., Chandel N.S. Mitochondrial Metabolism as a Target for Cancer Therapy. Cell Metab. 2020;32:341–352. doi: 10.1016/j.cmet.2020.06.019. - DOI - PMC - PubMed
    1. Skrtić M., Sriskanthadevan S., Jhas B., Gebbia M., Wang X., Wang Z., Hurren R., Jitkova Y., Gronda M., Maclean N., et al. Inhibition of Mitochondrial Translation as a Therapeutic Strategy for Human Acute Myeloid Leukemia. Cancer Cell. 2011;20:674–688. doi: 10.1016/j.ccr.2011.10.015. - DOI - PMC - PubMed
    1. Guo J.Y., Chen H.-Y., Mathew R., Fan J., Strohecker A.M., Karsli-Uzunbas G., Kamphorst J.J., Chen G., Lemons J.M.S., Karantza V., et al. Activated Ras Requires Autophagy to Maintain Oxidative Metabolism and Tumorigenesis. Genes Dev. 2011;25:460–470. doi: 10.1101/gad.2016311. - DOI - PMC - PubMed