PKB/Akt-dependent regulation of inflammation in cancer

Tang, Fengyuan; Wang, Yuhua; Hemmings, Brian A.; Rüegg, Curzio; Xue, Gui-Rong

doi:10.1016/j.semcancer.2017.04.018

Cited by 87 publications

(67 citation statements)

References 126 publications

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“…The nuclear transcription of NF-κB is activated via AKT signaling pathway under oxidative stress [39], which is independent of PI3K phosphorylation. The activation of these signaling pathways leads to the production of various proinflammatory mediators, such as TNF-α, IL-1β, IL-6, induced nitric oxide synthase (iNOS), and cyclooxygense-2 (COX-2), which are capable of amplifying the process of inflammation [40]. NF-κB is a highly inducible transcription factor that plays an important role in the hepatic acute phase response, innate/adaptive immunity, and cellular survival through the induction of genetic networks [41,42].…”

Section: Discussionmentioning

confidence: 99%

Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT/mTOR Pathways

Guo

Zhang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Hepatic ischemia-reperfusion (I/R) injury is a serious complication in patients who have undergone hepatic surgery such as orthotopic liver transplantation and partial hepatectomy. Recently, a new cytoprotective agent, ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), was reported to protect against hepatic I/R injury. However, the protective mechanism of UDCA-LPE is not fully understood. Therefore, we conducted this study to explore its underlying mechanism. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the liver lipid metabolism changes in mice during I/R. KEGG enrichment indicated that UDCA-LPE is likely to exert its protective role by regulating fatty acid (FA) metabolism. Further analysis found that UDCA-LPE significantly increased the ratio of oleic acid (OA) to palmitic acid (PA). We found that mice pretreated with OA improved tolerance to hepatic I/R injury. In addition, the phosphorylation level of AKT was markedly upregulated during oxidative stress to promote p65 nuclear translocation, triggering an inflammatory response that exacerbated cell damage and OA treatment significantly inhibited this process. Notably, OA was found to inhibit H2O2-induced oxidative stress, inflammation, and cell death in HepG2 cells. Furthermore, we found that OA supplementation to the medium did not result in a significant increase in intracellular OA, but marked increase in the ratio of OA to PA, which may be an important mechanism for the inflammatory response induced by oxidative stress during I/R. Finally, we demonstrated that OA increased the level of autophagy in HepG2 cells, which may be one of the protective mechanisms against oxidative stress. Collectively, this study revealed that FA metabolism functionally determines the oxidative stress-related inflammation caused by hepatic I/R. We hypothesize that OA treatment may be a promising strategy for preventing and treating I/R-induced liver damage.

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Section: Discussionmentioning

confidence: 99%

Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT/mTOR Pathways

Guo

Zhang

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…Cancer and diabetes are closely related to poorly regulated AKT activity. 58,59 AKT regulates cell cycle entry and survival via phosphorylation of forkhead box O, BCL2associated agonist of cell death, and glycogen synthase kinase 3 (GSK-3), thereby preventing cellular apoptosis through mammalian target of rapamycin activation. [57][58][59] Another vital protein that influences various cellular biological functions, such as cell motility, growth, differentiation, and membrane ruffle formation, which are mainly activated by EGFR, is phospholipase C-γ1 (PLC-γ1).…”

Section: The Egfr-related Pathwaymentioning

confidence: 99%

Comprehensive review of targeted therapy for colorectal cancer

Xie

Chen

Fang

2020

Sig Transduct Target Ther

1,126

821

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Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world and was responsible for nearly 881,000 cancer-related deaths in 2018. Surgery and chemotherapy have long been the first choices for cancer patients. However, the prognosis of CRC has never been satisfying, especially for patients with metastatic lesions. Targeted therapy is a new optional approach that has successfully prolonged overall survival for CRC patients. Following successes with the anti-EGFR (epidermal growth factor receptor) agent cetuximab and the anti-angiogenesis agent bevacizumab, new agents blocking different critical pathways as well as immune checkpoints are emerging at an unprecedented rate. Guidelines worldwide are currently updating the recommended targeted drugs on the basis of the increasing number of high-quality clinical trials. This review provides an overview of existing CRC-targeted agents and their underlying mechanisms, as well as a discussion of their limitations and future trends.

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“…Similarly, Xing, Jin, et al (2016) predicted the same outcome in RA-FLS cells from patients and proved that p38MAPK expression was found upregulated in comparison with osteoarthritic (OA) control cells. In par with these outcomes, IL-21 has recently been identified to activate MAPK signaling in fibroblasts and human derived peripheral blood monocytes (Vallieres & Girard, 2017;Wang et al, 2017). These evidences collectively provide insights into IL-21 mediated MAPK signaling pathway in immune cells of the RA synovium ( Figure 2).…”

Section: Mapk Signaling Pathwaymentioning

confidence: 81%

“…Phosphoinositide‐3 kinase (PI3K) and protein kinase B (Akt/PKB) signaling is involved in several cellular driven processes including cell survival and uncontrolled growth of cells (O'Donnell, Massi, Teng, & Mandala, ; Tang, Wang, Hemmings, Ruegg, & Xue, ). In RA pathogenesis, PI3K activation results in similar environment as witnessed in a cancer condition, promoting the survival of various immune cells such as: monocytes/macrophages, dendritic cells, and FLS in the joint space resulting in bone erosion and cartilage degradation (Malemud, , ).…”

Section: Introductionmentioning

confidence: 99%

Multifaceted role of IL‐21 in rheumatoid arthritis: Current understanding and future perspectives

Dinesh

Rasool²

2017

Journal Cellular Physiology

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Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder designated with hyperplastic synovium, bone destruction and cartilage degradation. Current therapies involve targeting major cytokines and inflammatory mediators involved in RA to alleviate the pain and provide a temporary relief. Interleukin 21 (IL-21), a recently identified cytokine is known to possess a versatile role in modulating the cells of the RA synovium. Over the past decade, the pleiotropic role of IL-21 in RA pathogenesis has been implicated in several aspects. T helper 17 (Th17) and follicular T helper cells (Tfh), being the key immunomodulators of the RA synovium secrete high amounts of IL-21 during disease progression. Several studies have provided experimental evidences elucidating the multifaceted role of IL-21 in RA disease progression. IL-21 has the potential to activate T cells, B cells, monocytes/macrophages and synovial fibroblasts in RA pathogenesis through activation of JAK-STAT, MAPK and PI3K/Akt signaling pathways. Till date, therapies targeting Th17 cells and its inflammatory cytokines have been under investigation and are subjected to various clinical trials. This review showcases the role of IL-21 in RA pathogenesis and recent reports implicating its function in various immune cells, major signaling pathways, and in promoting osteoclastogenesis.

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PKB/Akt-dependent regulation of inflammation in cancer

Cited by 87 publications

References 126 publications

Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT/mTOR Pathways

Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT/mTOR Pathways

Comprehensive review of targeted therapy for colorectal cancer

Multifaceted role of IL‐21 in rheumatoid arthritis: Current understanding and future perspectives

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