Role of <scp>FOXO</scp> protein's abnormal activation through <scp>PI3K</scp>/<scp>AKT</scp> pathway in platinum resistance of ovarian cancer

Shi, Yun-Yue; Meng, Xiang-Tian; Xu, Yanan; Tian, Xiujuan

doi:10.1111/jog.14753

Cited by 12 publications

(6 citation statements)

References 129 publications

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“…Also, in COPD airway epithelial cells, the aberrant activity of EGFR increases PI3K/ Akt-mediated phosphorylation of FoxO3A, which increases the expression of chemokines and IL8. 39 PI3K agitates AKT, which in turn regulates FoxO signaling to reduce drug resistance, 40 exerts anti-apoptotic effects, 41 and regulates the cell cycle. 42 The multifunctional activity of AKT coordinates cellular mechanisms, such as oxidative stress 43 and inflammation, closely related to the destructive pathogenesis of COPD.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Molecular Mechanism of Xuebijing Injection in the Treatment of Chronic Obstructive Pulmonary Disease by Combining Network Pharmacology and Affymetrix Array

Lin

Zhang

et al. 2022

Natural Product Communications

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Xuebijing injection (XBJ), one of the classical prescriptions for treating inflammation-related diseases, has been used to chronic obstructive pulmonary disease (COPD) in clinical practice. However, its molecular mechanism is still unclear. Network pharmacology combined with Affymetrix arrays and molecular docking techniques were applied to explore the molecular mechanism of XBJ for COPD. Predictive analysis of 728 active compounds in XBJ and 6 sets of Affymetrix arrays expression data resulted in 106 potential therapeutic targets. Next, based on the active compound-co-target network topology analysis, most of these targets were found to be modulated by quercetin, myricetin, and ellagic acid. Furthermore, protein–protein interaction (PPI) analysis revealed that the key targets may be EGFR, STAT3, AKT1, CCND1, MMP9, AR, ESR1, and PTGS2. Then, by constructing a component-target-pathway network, we found that XBJ was a multi-pathway, multi-target, multi-compound synergistic therapy for COPD, and four key targets were involved in the FoxO signaling pathway. Luteolin and salvianolic acid b had the optimal binding ability to several key proteins. Therefore, we hypothesize that quercetin, myricetin, ellagic acid, luteolin, and salvianolic acid b mainly contribute to the therapeutic effect of XBJ on COPD by modulating the FoxO signaling pathway by regulating EGFR, STAT3, AKT1, and CCND1. XBJ exerts anti-inflammatory and antioxidative stress effects through the PI3K/Akt/FoxO axis combined with MMP9, AR, ESR1, and PTGS2 to regulate other signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Unraveling the Molecular Mechanism of Xuebijing Injection in the Treatment of Chronic Obstructive Pulmonary Disease by Combining Network Pharmacology and Affymetrix Array

Lin

Zhang

et al. 2022

Natural Product Communications

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“…The significant dysregulation of ATM interactome components Atmin, Nr4a1 and Foxo3/Foxo1 (but not the ATM interactome components Mre11/Rad50/Nbs1, nor its downstream effectors Chk2 and Tp53) argued against neural ATM functions at this cerebellar age in DNA damage repair, instead suggesting osmotic/oxidative/nutrient stress [83][84][85]. Interestingly however, the deubiquitinase USP2 was reported recently to function in the ATM/NBS1 interactome [86], and showed strong downregulation within the ATM-null cerebellar transcriptome.…”

Section: The Cerebellar Transcriptome Profile Of Atm-null Mice At 12 ...mentioning

confidence: 99%

In Cerebellar Atrophy of 12-Month-Old ATM-Null Mice, Transcriptome Upregulations Concern Most Neurotransmission and Neuropeptide Pathways, While Downregulations Affect Prominently Itpr1, Usp2 and Non-Coding RNA

Reichlmeir,

Canet-Pons,

Koepf

et al. 2023

Cells

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The autosomal recessive disorder Ataxia-Telangiectasia is caused by a dysfunction of the stress response protein, ATM. In the nucleus of proliferating cells, ATM senses DNA double-strand breaks and coordinates their repair. This role explains T-cell dysfunction and tumour risk. However, it remains unclear whether this function is relevant for postmitotic neurons and underlies cerebellar atrophy, since ATM is cytoplasmic in postmitotic neurons. Here, we used ATM-null mice that survived early immune deficits via bone-marrow transplantation, and that reached initial neurodegeneration stages at 12 months of age. Global cerebellar transcriptomics demonstrated that ATM depletion triggered upregulations in most neurotransmission and neuropeptide systems. Downregulated transcripts were found for the ATM interactome component Usp2, many non-coding RNAs, ataxia genes Itpr1, Grid2, immediate early genes and immunity factors. Allelic splice changes affected prominently the neuropeptide machinery, e.g., Oprm1. Validation experiments with stressors were performed in human neuroblastoma cells, where ATM was localised only to cytoplasm, similar to the brain. Effect confirmation in SH-SY5Y cells occurred after ATM depletion and osmotic stress better than nutrient/oxidative stress, but not after ATM kinase inhibition or DNA stressor bleomycin. Overall, we provide pioneer observations from a faithful A-T mouse model, which suggest general changes in synaptic and dense-core vesicle stress adaptation.

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“…The FOXO subgroup, which includes FOXO1, FOXO3A, FOXO4, and FOXO6, play crucial roles as negative regulators of both cell proliferation and survival [136][137][138]. These proteins promote cell cycle arrest at the G1 phase, initiate apoptosis, and facilitate DNA repair processes [139][140][141]. Hence, they are recognized as genuine tumor suppressors.…”

Section: Forkhead Box (Fox) Of Transcription Factorsmentioning

confidence: 99%

EWS/FLI1 Characterization, Activation, Repression, Target Genes and Therapeutic Opportunities in Ewing Sarcoma

Yasir,

Park,

Chun

2023

IJMS

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Despite their clonal origins, tumors eventually develop into complex communities made up of phenotypically different cell subpopulations, according to mounting evidence. Tumor cell-intrinsic programming and signals from geographically and temporally changing microenvironments both contribute to this variability. Furthermore, the mutational load is typically lacking in childhood malignancies of adult cancers, and they still exhibit high cellular heterogeneity levels largely mediated by epigenetic mechanisms. Ewing sarcomas represent highly aggressive malignancies affecting both bone and soft tissue, primarily afflicting adolescents. Unfortunately, the outlook for patients facing relapsed or metastatic disease is grim. These tumors are primarily fueled by a distinctive fusion event involving an FET protein and an ETS family transcription factor, with the most prevalent fusion being EWS/FLI1. Despite originating from a common driver mutation, Ewing sarcoma cells display significant variations in transcriptional activity, both within and among tumors. Recent research has pinpointed distinct fusion protein activities as a principal source of this heterogeneity, resulting in markedly diverse cellular phenotypes. In this review, we aim to characterize the role of the EWS/FLI fusion protein in Ewing sarcoma by exploring its general mechanism of activation and elucidating its implications for tumor heterogeneity. Additionally, we delve into potential therapeutic opportunities to target this aberrant fusion protein in the context of Ewing sarcoma treatment.

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Role of FOXO protein's abnormal activation through PI3K/AKT pathway in platinum resistance of ovarian cancer

Cited by 12 publications

References 129 publications

Unraveling the Molecular Mechanism of Xuebijing Injection in the Treatment of Chronic Obstructive Pulmonary Disease by Combining Network Pharmacology and Affymetrix Array

Unraveling the Molecular Mechanism of Xuebijing Injection in the Treatment of Chronic Obstructive Pulmonary Disease by Combining Network Pharmacology and Affymetrix Array

In Cerebellar Atrophy of 12-Month-Old ATM-Null Mice, Transcriptome Upregulations Concern Most Neurotransmission and Neuropeptide Pathways, While Downregulations Affect Prominently Itpr1, Usp2 and Non-Coding RNA

EWS/FLI1 Characterization, Activation, Repression, Target Genes and Therapeutic Opportunities in Ewing Sarcoma

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