Energy Metabolism in Cancer: The Roles of STAT3 and STAT5 in the Regulation of Metabolism-Related Genes

Valle‐Mendiola, Arturo; Soto‐Cruz, Isabel

doi:10.3390/cancers12010124

Cited by 55 publications

(41 citation statements)

References 181 publications

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“…Previous studies have demonstrated that abnormal metabolism is one of the markers of cancer cells, and that there are differences between healthy and tumor cells in energy metabolism (58)(59)(60); in addition, various catabolic pathways, for example, glycolysis, OXPHOS and fatty acid metabolism, are involved in energy metabolism (61). In the current study, RNA-seq data were used to detect local energy metabolism-related gene expression status and their prognostic value for patients with ovarian cancer.…”

Section: Discussionmentioning

confidence: 94%

Identification of an energy metabolism‑related gene signature in ovarian cancer prognosis

Wang

2020

Oncol Rep

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Changes in energy metabolism may be potential biomarkers and therapeutic targets for cancer as they frequently occur within cancer cells. However, basic cancer research has failed to reach a consistent conclusion on the function(s) of mitochondria in energy metabolism. The significance of energy metabolism in the prognosis of ovarian cancer remains unclear; thus, there remains an urgent need to systematically analyze the characteristics and clinical value of energy metabolism in ovarian cancer. Based on gene expression patterns, the present study aimed to analyze energy metabolism-associated characteristics to evaluate the prognosis of patients with ovarian cancer. A total of 39 energy metabolism-related genes significantly associated with prognosis were obtained, and three molecular subtypes were identified by nonnegative matrix factorization clustering, among which the C1 subtype was associated with poor clinical outcomes of ovarian cancer. The immune response was enhanced in the tumor microenvironment. A total of 888 differentially expressed genes were identified in C1 compared with the other subtypes, and the results of the pathway enrichment analysis demonstrated that they were enriched in the 'PI3K-Akt signaling pathway', 'cAMP signaling pathway', 'ECM-receptor interaction' and other pathways associated with the development and progression of tumors. Finally, eight characteristic genes (tolloid-like 1 gene, type XVI collagen, prostaglandin F2α, cartilage intermediate layer protein 2, kinesin family member 26b, interferon inducible protein 27, growth arrest-specific gene 1 and chemokine receptor 7) were obtained through LASSO feature selection; and a number of them have been demonstrated to be associated with ovarian cancer progression. In addition, Cox regression analysis was performed to establish an 8-gene signature, which was determined to be an independent prognostic factor for patients with ovarian cancer and could stratify sample risk in the training, test and external validation datasets (P<0.01; AUC >0.8). Gene Set Enrichment Analysis results revealed that the 8-gene signature was involved in important biological processes and pathways of ovarian cancer. In conclusion, the present study established an 8-gene signature associated with metabolic genes, which may provide new insights into the effects of energy metabolism on ovarian cancer. The 8-gene signature may serve as an independent prognostic factor for ovarian cancer patients.

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Section: Discussionmentioning

confidence: 94%

Identification of an energy metabolism‑related gene signature in ovarian cancer prognosis

Wang

2020

Oncol Rep

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“…The results from several studies indicate that STAT3 functions as an integration center for various cancer cell signals through its nuclear and mitochondrial activities. In recent years, a pro-oncogenic role for STAT3 serine phosphorylation has been widely reported, and is also reported to be associated with its functions in the mitochondria [ 111 ]. However, the mechanism by which STAT3 carries out its activities within the mitochondria remains unknown and controversial.…”

Section: Discussionmentioning

confidence: 99%

Perspectives Regarding the Intersections between STAT3 and Oxidative Metabolism in Cancer

Chun

Jang

Kim

2020

Cells

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Signal transducer and activator of transcription 3 (STAT3) functions as a major molecular switch that plays an important role in the communication between cytokines and kinases. In this role, it regulates the transcription of genes involved in various biochemical processes, such as proliferation, migration, and metabolism of cancer cells. STAT3 undergoes diverse post-translational modifications, such as the oxidation of cysteine by oxidative stress, the acetylation of lysine, or the phosphorylation of serine/threonine. In particular, the redox modulation of critical cysteine residues present in the DNA-binding domain of STAT3 inhibits its DNA-binding activity, resulting in the inactivation of STAT3-mediated gene expression. Accumulating evidence supports that STAT3 is a key protein that acts as a mediator of metabolism and mitochondrial activity. In this review, we focus on the post-translational modifications of STAT3 by oxidative stress and how the modification of STAT3 regulates cell metabolism, particularly in the metabolic pathways in cancer cells.

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“…In fact, multiple studies have demonstrated that in the absence of a given STAT member, receptors will recruit other STAT members instead (Hennighausen et al, 2018;Yu et al, 2010;Valle & Soto et al, 2020;Hosui et al, 2009;Hin et al, 2020;Friedbichler et al, 2012). STAT5 and STAT3 are two proteins of STAT family that show high homology in their functional domains, can be activated by different mechanisms, and bind to distinct loci to regulate specific target gene expression .…”

Section: Discussionmentioning

confidence: 99%

STAT3 but not STAT5 contributes to the protective effect of electro-acupuncture against myocardial ischemia/reperfusion injury

Guo

Jing

Chen³

et al. 2020

Preprint

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Late remote ischemia preconditioning (RIPC) and electro-acupuncture (EA) have both been suggested to reduce injury caused by myocardial ischemia/reperfusion (I/R). Our previous study has found that cardioprotection in RIPC is STAT5-dependent. Here, we aim to observe the effects of electro-acupuncture pretreatment (EAP) on I/R in the presence or absence of STAT5 in mice and investigate whether the protection of EAP is in a STAT5-dependent manner. In this study, EAP decreased myocardial infarction size (IS) /total area (TA) and rate of cardiomyocyte apoptosis. STAT5 was activated by EAP in the Stat5fl/fl mice but not in the Stat5-cKO mice, whereas, STAT3 was activated by EAP only in the Stat5-cKO but not in the Stat5fl/fl mice. Differentially expressed genes (DEGs) regulated by EAP in the Stat5fl/fl and the Stat5-cKO mice were quite distinct, indicating that EAP may activate IL-6/STAT3 signal in the absence of Stat5, and that EAP-induced cardioprotection against myocardial I/R injury was correlated with the activation of anti-apoptotic signaling and cardiomyocyte-survival signaling. Our results, for the first time, demonstrated that the protective effect of EAP was attributed to, but not dependent on, STAT5.

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Energy Metabolism in Cancer: The Roles of STAT3 and STAT5 in the Regulation of Metabolism-Related Genes

Cited by 55 publications

References 181 publications

Identification of an energy metabolism‑related gene signature in ovarian cancer prognosis

Identification of an energy metabolism‑related gene signature in ovarian cancer prognosis

Perspectives Regarding the Intersections between STAT3 and Oxidative Metabolism in Cancer

STAT3 but not STAT5 contributes to the protective effect of electro-acupuncture against myocardial ischemia/reperfusion injury

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