Mitogen-Activated Protein Kinase (MAPK) and Obesity-Related Cancer

Donohoe, Fionán; Wilkinson, Michael; Baxter, Eva; Brennan, Donal J.

doi:10.3390/ijms21041241

Cited by 59 publications

(42 citation statements)

References 169 publications

(181 reference statements)

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“…Furthermore, αT may also act to inhibit pathways that are activated by ROS such as p38 MAPK ( Schett et al., 2008 ; Thalhamer et al., 2008 ; Wang et al., 2011 ; Wong et al., 2017 ). These pathways tend to be elevated in obese individuals, various inflammatory pathologies and are diminished with αT supplementation ( Wong et al., 2017 ; Donohoe et al., 2020 ). Administration of αT in obese individual induces differentiation of macrophages toward an M2 phenotype that exhibits anti-inflammatory effects ( Alcala et al., 2015 ; Ray et al., 2016 ).…”

Section: Antioxidants In Ameliorating Obesity and Associated Comorbidmentioning

confidence: 99%

Therapeutic Efficacy of Antioxidants in Ameliorating Obesity Phenotype and Associated Comorbidities

et al. 2020

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Obesity has been a worldwide epidemic for decades. Despite the abundant increase in knowledge regarding the etiology and pathogenesis of obesity, the prevalence continues to rise with estimates predicting considerably higher numbers by the year 2030. Obesity is characterized by an abnormal lipid accumulation, however, the physiological consequences of obesity are far more concerning. The development of the obesity phenotype constitutes dramatic alterations in adipocytes, along with several other cellular mechanisms which causes substantial increase in systemic oxidative stress mediated by reactive oxygen species (ROS). These alterations promote a chronic state of inflammation in the body caused by the redox imbalance. Together, the systemic oxidative stress and chronic inflammation plays a vital role in maintaining the obese state and exacerbating onset of cardiovascular complications, Type II diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, and other conditions where obesity has been linked as a significant risk factor. Because of the apparent role of oxidative stress in the pathogenesis of obesity, there has been a growing interest in attenuating the pro-oxidant state in obesity. Hence, this review aims to highlight the therapeutic role of antioxidants, agents that negate pro-oxidant state of cells, in ameliorating obesity and associated comorbidities. More specifically, this review will explore how various antioxidants target unique and diverse pathways to exhibit an antioxidant defense mechanism.

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Section: Antioxidants In Ameliorating Obesity and Associated Comorbidmentioning

confidence: 99%

Therapeutic Efficacy of Antioxidants in Ameliorating Obesity Phenotype and Associated Comorbidities

et al. 2020

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“…The P38 mitogen-activated protein kinase (MAPK) pathway activation results in cell apoptosis in EC. 27 Emerging evidence suggests that the activation of p38 MAPK is mediated by ferroptosis. 28 , 29 To explore the role p-p38 played in PTPN18 mediated ferroptosis, we measured the expression of p-p38 after silencing the expression of PTPN18.…”

Section: Discussionmentioning

confidence: 99%

Silencing of PTPN18 Induced Ferroptosis in Endometrial Cancer Cells Through p-P38-Mediated GPX4/xCT Down-Regulation

Wang¹,

Peng²,

Cai³

et al. 2021

CMAR

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Background Endometrial cancer (EC) is the fourth most common neoplasm and the eighth leading cause of cancer death in females worldwide. PTPN18 is a member of the protein tyrosine phosphatases (PTP) family, which is associated with the occurrence and progression of various human cancers. PTPN18 was up-regulated in endometrial cancer tissues and high level of PTPN18 promoted proliferation and metastasis of EC cells. Methods The expression of PTPN18, GPX4 and xCT in endometrial cancer tissues and KLE cells was detected by immunohistochemistry and Western blot, respectively. Lentiviral transfection were used to silence PTPN18 level in KLE cells. The Ros level in KLE cells was examined by ELISA assay. Results In the present study, we found that silencing of PTPN18 induced ferroptosis in KLE endometrial cancer cells. PTPN18 knockdown increased intracellular ROS level and down-regulated GPX4 and xCT expression. Besides, silencing of PTPN18 also induced the expression of p-p38. Conclusion We concluded that silencing of PTPN18 might induce ferroptosis by targeting the p-p38/GPX4/xCT axis. The results provide critical insight into the application of PTPN18 knockdown in EC intervention.

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“…In the literature, development of insulin resistance and hyperinsulinemia has been shown as a clear link between adipose tissue expansion and etiology of diseases like obesity, type-2 diabetes and cancer [31]. Likewise, the implication of MAPK signaling in obesity-related immune paralysis and cancer has been reviewed very recently [32]. Another top significant pathway, JAK/STAT signaling pathway in (Table 2) is a highly conserved functional pathway required for normal homeostasis which, when dysregulated, contributes to the development of obesity and diabetes [33].…”

Section: Discussionmentioning

confidence: 99%

Global Gene Expression Profiling of Body-Mass Index in Middle-Aged Danish Twins

Baumbach

Mohammadnejad³

et al. 2020

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Objective: The body mass index (BMI) measured as weight in relation to height is an important monitor for obesity and diabetes, with individual variation under control by genetic and environmental factors. In transcriptome-wide association studies on BMI, the genetic contribution calls for controlling of genetic confounding that affects both BMI and gene expression. We performed a global gene expression profiling of BMI on peripheral blood cells using monozygotic twins for efficient handling of genetic make-ups. Methods: We applied a generalized association method to genome-wide gene expression data on 229 pairs of monozygotic twins (age 56-80 years) for detecting diverse patterns of correlation between BMI and gene expression. Results: We detected seven probes associated with BMI with p<1e-04, among them two probes with p<1e05 (p=2.83e-06 AAK1; p=7.83e-06 LILRA3). In total, the analysis found 1579 probes with nominal p<0.05. Biological pathway analysis of enriched pathways found 50 KEGG and 45 Reactome pathways (FDR<0.05). The identified top functional pathways included immune function, JAK-STAT signalling, insulin signalling and regulation of energy metabolism. Conclusion: This transcriptome-wide association study using monozygotic twins and generalized correlation identified differentially expressed genes and a broad spectrum of enriched biological pathways that may implicate metabolic health.

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Mitogen-Activated Protein Kinase (MAPK) and Obesity-Related Cancer

Cited by 59 publications

References 169 publications

Therapeutic Efficacy of Antioxidants in Ameliorating Obesity Phenotype and Associated Comorbidities

Therapeutic Efficacy of Antioxidants in Ameliorating Obesity Phenotype and Associated Comorbidities

Silencing of PTPN18 Induced Ferroptosis in Endometrial Cancer Cells Through p-P38-Mediated GPX4/xCT Down-Regulation

Global Gene Expression Profiling of Body-Mass Index in Middle-Aged Danish Twins

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