PMID- 30254608
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 9
DP  - 2018
TI  - Cholesterol as an Endogenous ERRalpha Agonist: A New Perspective to Cancer Treatment.
PG  - 525
LID - 10.3389/fendo.2018.00525 [doi]
LID - 525
AB  - The estrogen-related receptors (ERRs) are important members of nuclear receptors 
      which contain three isoforms (alpha, beta, and gamma). ERRalpha is the best-characterized 
      isoform expressed mainly in high-energy demanding tissues where it preferentially 
      works in association with the peroxisome proliferator-activated receptor-gamma 
      co-activator 1alpha (PGC-1alpha) and PGC-1beta. ERRalpha together with its cofactors modulates 
      cellular metabolism, supports the growth of rapidly dividing cells, directs 
      metabolic programs required for cell differentiation and maintains cellular 
      energy homeostasis in differentiated cells. In cancer cells, the functional 
      association between ERRalpha and PGC-1s is further influenced by oncogenic signals 
      and induces metabolic programs favoring cell growth and proliferation as well as 
      tumor progression. Recently, cholesterol has been identified as a natural ERRalpha 
      ligand using a combined biochemical strategy. This new finding highlighted some 
      important physiological aspects related to the use of cholesterol-lowering drugs 
      such as statins and bisphosphonates. Even more meaningful is the link between 
      increased cholesterol levels and certain cancer phenotypes characterized by an 
      overexpressed ERRalpha such as mammary, prostatic, and colorectal cancers, where the 
      metabolic adaptation affects many cancer processes. Moreover, high-energy 
      demanding cancer-related processes are strictly related to the cross-talk between 
      tumor cells and some key players of tumor microenvironment, such as 
      tumor-associated macrophage that fuels cancer progression. Some evidence suggests 
      that high cholesterol content and ERRalpha activity favor the inflammatory 
      environment by the production of different cytokines. In this review, starting 
      from the most recent observations on the physiological role of the new signaling 
      activated by the natural ligand of ERRalpha, we propose a new hypothesis on the 
      suitability to control cholesterol levels as a chance in modulating ERRalpha activity 
      in those tumors in which its expression and activity are increased.
FAU - Casaburi, Ivan
AU  - Casaburi I
AD  - Department of Pharmacy and Health and Nutritional Science, University of 
      Calabria, Cosenza, Italy.
FAU - Chimento, Adele
AU  - Chimento A
AD  - Department of Pharmacy and Health and Nutritional Science, University of 
      Calabria, Cosenza, Italy.
FAU - De Luca, Arianna
AU  - De Luca A
AD  - Department of Pharmacy and Health and Nutritional Science, University of 
      Calabria, Cosenza, Italy.
FAU - Nocito, Marta
AU  - Nocito M
AD  - Department of Pharmacy and Health and Nutritional Science, University of 
      Calabria, Cosenza, Italy.
FAU - Sculco, Sara
AU  - Sculco S
AD  - Department of Pharmacy and Health and Nutritional Science, University of 
      Calabria, Cosenza, Italy.
FAU - Avena, Paola
AU  - Avena P
AD  - Department of Pharmacy and Health and Nutritional Science, University of 
      Calabria, Cosenza, Italy.
FAU - Trotta, Francesca
AU  - Trotta F
AD  - Department of Pharmacy and Health and Nutritional Science, University of 
      Calabria, Cosenza, Italy.
FAU - Rago, Vittoria
AU  - Rago V
AD  - Department of Pharmacy and Health and Nutritional Science, University of 
      Calabria, Cosenza, Italy.
FAU - Sirianni, Rosa
AU  - Sirianni R
AD  - Department of Pharmacy and Health and Nutritional Science, University of 
      Calabria, Cosenza, Italy.
FAU - Pezzi, Vincenzo
AU  - Pezzi V
AD  - Department of Pharmacy and Health and Nutritional Science, University of 
      Calabria, Cosenza, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180911
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
PMC - PMC6141749
OTO - NOTNLM
OT  - ERRalpha
OT  - IL-8
OT  - adrenocortical carcinoma (ACC)
OT  - breast and prostate cancer
OT  - cancer metabolism
OT  - cholesterol
OT  - colonrectal cancer
EDAT- 2018/09/27 06:00
MHDA- 2018/09/27 06:01
PMCR- 2018/01/01
CRDT- 2018/09/27 06:00
PHST- 2018/06/08 00:00 [received]
PHST- 2018/08/21 00:00 [accepted]
PHST- 2018/09/27 06:00 [entrez]
PHST- 2018/09/27 06:00 [pubmed]
PHST- 2018/09/27 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2018.00525 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2018 Sep 11;9:525. doi: 10.3389/fendo.2018.00525. 
      eCollection 2018.