Melanoma—Time to fast or time to feast? An interplay between PPARs, metabolism and immunity
Maja Grabacka , Przemysław M. Płonka , Krzysztof Reiss
AbstractDevelopment and progression of melanoma can be accelerated by intensification of particular metabolic pathways, such as aerobic glycolysis and avid amino acid catabolism, and is accompanied by aberrant immune responses within the tumor microenvironment. Contrary to other cancer types, melanoma reveals some unique tissue‐specific features, such as melanogenesis, which is intertwined with metabolism. Nuclear peroxisome proliferator‐activated receptors (PPARs) take part in regulation of systemic and cellular metabolism, inflammation and melanogenesis. They appear as a focal regulatory point for these three distinct processes by occupying the intersection among AMP‐dependent protein kinase (AMPK), mammalian target of rapamycin (mTOR) and PPAR gamma coactivator 1‐alpha (PGC‐1α) signalling pathways. When deregulated, they may accelerate melanoma malignant growth. Presenting the contribution of PPARα and PPARγ in melanoma biology, we attempt to ask how two contrasting metabolic states: obesity and fasting, can change progression of the disease and possible outcome of the treatment. This short essay is aimed to provoke a discussion about some practical implications for melanoma prevention and treatment, especially: how metabolic manipulation may be exploited to overcome immunosuppression and support immune checkpoint blockade efficacy.
|Journal series||Experimental Dermatology, ISSN 0906-6705, e-ISSN 1600-0625, (N/A 100 pkt)|
|Publication size in sheets||0.5|
|Keywords in English||AMP‐dependent protein kinase (AMPK), inflammasome, ketone bodies, mammalian target of rapamycin, signal transducer and activator of transcription|
|ASJC Classification||; ;|
|Publication indicators||: 2018 = 0.896; : 2018 = 2.868 (2) - 2018=2.68 (5)|
|Finansowanie||The Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University was a partner of the Leading National Research Center (KNOW) supported by the Polish Ministry of Science and Higher Education. The paper was partially supported from this grant (KNOW 35p/10/2015 to PMP). KR is supported by the grant 1P20 GM121288‐02|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.