Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) Signaling Regulates Mitochondrial Biogenesis and Respiration via Estrogen-related Receptor α (ERRα)

Yang, Li; He, Liyun; Zeng, Ni; Sahu, Divya; Cadenas, Enrique; Shearn, Colin T.; Li, Wei; Stiles, Bangyan L.

doi:10.1074/jbc.m113.450353

Cited by 53 publications

(57 citation statements)

References 66 publications

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“…Increased protein synthesis can be induced by the PTEN/PI3K/Akt/mTOR pathway, deregulation of which is often detected in most clinical prostate cancer. Although no direct evidence of correlation is shown between the PTEN loss and ERRα activation in prostate cancer cells, liver-specific deletion of PTEN in hepatocytes can induce increased mitochondrial respiration and enhanced glycolysis (similar to the Warburg effect), which is accompanied with upregulation of ERRα [62], This negative correlation between expressions of ERRα and PTEN is also observed in human liver cancer. Moreover, the ERRα induction in Pten-null hepatocytes can promote the transformation and growth potential of these cells [62].…”

Section: Errsmentioning

confidence: 84%

“…Although no direct evidence of correlation is shown between the PTEN loss and ERRα activation in prostate cancer cells, liver-specific deletion of PTEN in hepatocytes can induce increased mitochondrial respiration and enhanced glycolysis (similar to the Warburg effect), which is accompanied with upregulation of ERRα [62], This negative correlation between expressions of ERRα and PTEN is also observed in human liver cancer. Moreover, the ERRα induction in Pten-null hepatocytes can promote the transformation and growth potential of these cells [62]. It is speculated that such a negative correlation between ERRα and PTEN signaling may also occur in the energy reprogramming in prostate cancer, as PTEN protein is reduced or absent in two-thirds of the clinical tumors.…”

Section: Errsmentioning

confidence: 84%

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The emerging roles of orphan nuclear receptors in prostate cancer

Cheung

Wang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Orphan nuclear receptors are members of the nuclear receptor (NR) superfamily and are so named because their endogenous physiological ligands are either unknown or may not exist. Because of their important regulatory roles in many key physiological processes, dysregulation of signalings controlled by these receptors is associated with many diseases including cancer. Over years, studies of orphan NRs have become an area of great interest because their specific physiological and pathological roles have not been well-defined, and some of them are promising drug targets for diseases. The recently identified synthetic small molecule ligands, acting as agonists or antagonists, to these orphan NRs not only help to understand better their functional roles but also highlight that the signalings mediated by these ligand-independent NRs in diseases could be therapeutically intervened. This review is a summary of the recent advances in elucidating the emerging functional roles of orphan NRs in cancers, especially prostate cancer. In particular, some orphan NRs, RORγ, TR2, TR4, COUP-IFII, ERRα, DAX1 and SHP, exhibit crosstalk or interference with androgen receptor (AR) signaling in either normal or malignant prostatic cells, highlighting their involvement in prostate cancer progression as androgen and AR signaling pathway play critical roles in this process. We also propose that a better understanding of the mechanism of actions of these orphan NRs in prostate gland or prostate cancer could help to evaluate their potential value as therapeutic targets for prostate cancer.

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Section: Errsmentioning

confidence: 84%

Section: Errsmentioning

confidence: 84%

The emerging roles of orphan nuclear receptors in prostate cancer

Cheung

Wang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…Increased mitochondrial oxidation in adipose tissue by Tfam knockout increases energy expenditure and protects mice against obesity and insulin resistance, also in a UCP1-independent manner 35 . 36 . Activation of PI3K/Akt by PTEN deletion is associated with increased mitochondrial mass and respiration 36 .…”

Section: Discussionmentioning

confidence: 99%

“…36 . Activation of PI3K/Akt by PTEN deletion is associated with increased mitochondrial mass and respiration 36 . p38 MAPK and Ca 2 þ signalling has been shown to drive activation of Ppargc1a transcription by exercise and cold 11 , and stimulation of SCF/Kit is known to activate p38 and Ca 2 þ mobilization 22 .…”

Section: Discussionmentioning

confidence: 99%

The stem cell factor/Kit signalling pathway regulates mitochondrial function and energy expenditure

Huang

Ruan

et al. 2014

Nat Commun

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Cell growth is tightly coupled with mitochondrial biogenesis in order to maintain energy and organelle homeostasis. Receptor tyrosine kinase Kit and its ligand, stem cell factor (SCF), play a critical role in the growth and survival of multiple cell lineages. Here we report that the expression of SCF and Kit in adipose tissues is responsive to food availability and environmental temperature, and is altered in obese mice and human patients. Mice carrying a lossof-function mutation in Kit develop obesity as a result of decreased energy expenditure. These phenotypes are associated with reduced PGC-1a expression and mitochondrial dysfunction in brown adipose tissue and skeletal muscle. We further demonstrate that SCF/Kit directly promotes Ppargc1a transcription and mitochondrial biogenesis. Blocking Kit signalling in mice decreases PGC-1a expression and thermogenesis, while overexpressing SCF systemically or specifically in brown adipose tissue increases thermogenesis and reduces weight gain. Collectively, these data provide mechanistic insight into the regulation of mitochondrial function by SCF/Kit signalling and lay a foundation for exploring SCF/Kit signalling as a therapeutic target for metabolic diseases.

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“…Cellular ROS was measured according to published protocols (78,79). Briefly, cells were washed with PBS and incubated with 5 μM CM-H2DCFDA (Life Technologies) for 30 minutes.…”

mentioning

confidence: 99%