HPV-induced Nurr1 promotes cancer aggressiveness, self-renewal, and radioresistance via ERK and AKT signaling in cervical cancer

Wan, Peter Kok-Ting; Leung, Thomas; Siu, Michelle K.Y.; Mo, Xue-Tang; Tang, Hermit Wai-Man; Chan, Ki; Cheung, Annie Nga‐Yin; Ngan, Hextan Y. S.

doi:10.1016/j.canlet.2020.09.025

Cited by 18 publications

(14 citation statements)

References 56 publications

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“…mTOR and ERK are two downstream pathways of KRAS, which are essential for PDAC cell proliferation, and the inhibition of either pathway might induce the hyperactivation of the other one. 25 , 26 In our study, ibr‐7 substantially abrogated the activation of both mTOR and ERK signalling pathway, resulting in its superior anti‐proliferation activity than ibrutinib. The activation of mTOR pathway might influence mitochondrial proteins and protect cells from mitochondrial‐dependent apoptosis.…”

Section: Discussionmentioning

confidence: 50%

“…To explore the underlying mechanisms, we examined key proteins that are closely correlated with cell survival. mTOR and ERK are two downstream pathways of KRAS, which are essential for PDAC cell proliferation, and the inhibition of either pathway might induce the hyperactivation of the other one 25,26 . In our study, ibr‐7 substantially abrogated the activation of both mTOR and ERK signalling pathway, resulting in its superior anti‐proliferation activity than ibrutinib.…”

Section: Discussionmentioning

confidence: 51%

“…To explore the underlying the other one. 25,26 In our study, ibr-7 substantially abrogated the activation of both mTOR and ERK signalling pathway, resulting in its superior anti-proliferation activity than ibrutinib. The activation of mTOR pathway might influence mitochondrial proteins and protect cells from mitochondrial-dependent apoptosis.…”

Section: Trim32 Played a Key Role In The Progression Of Pdac Cellsmentioning

confidence: 56%

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Inhibition of TRIM32 by ibr‐7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway

Zhang

Yan

et al. 2021

J Cellular Molecular Medi

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Pancreatic cancer is one of the most notorious diseases for being asymptomatic at early stage and high mortality rate thereafter. However, either chemotherapy or targeted therapy has rarely achieved success in recent clinical trials for pancreatic cancer. Novel therapeutic regimens or agents are urgently in need. Ibr‐7 is a novel derivative of ibrutinib, displaying superior antitumour activity in pancreatic cancer cells than ibrutinib. In vitro studies showed that ibr‐7 greatly inhibited the proliferation of BxPC‐3, SW1990, CFPAC‐1 and AsPC‐1 cells via the induction of mitochondrial‐mediated apoptosis and substantial suppression of mTOR/p70S6K pathway. Moreover, ibr‐7 was able to sensitize pancreatic cancer cells to gemcitabine through the efficient repression of TRIM32, which was positively correlated with the proliferation and invasiveness of pancreatic cancer cells. Additionally, knockdown of TRIM32 diminished mTOR/p70S6K activity in pancreatic cancer cells, indicating a positive feedback loop between TRIM32 and mTOR/p70S6K pathway. To conclude, this work preliminarily explored the role of TRIM32 in the malignant properties of pancreatic cancer cells and evaluated the possibility of targeting TRIM32 to enhance effectiveness of gemcitabine, thereby providing a novel therapeutic target for pancreatic cancer.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 51%

Section: Trim32 Played a Key Role In The Progression Of Pdac Cellsmentioning

confidence: 56%

See 1 more Smart Citation

Inhibition of TRIM32 by ibr‐7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway

Zhang

Yan

et al. 2021

J Cellular Molecular Medi

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“…Trametinib is a reversible, highly selective allosteric inhibitor of MEK1/MEK2 activation. Relevant research showed, trametinib combined with PI3K/mTOR dual inhibitor dactylitis can eliminate the enhancement of nuclear receptor related-1 protein (Nurr1) to cervical cancer cell aggressiveness by upregulating p21 and p27 expression and inhibiting MMP9 and KLF4 expression ( Wan et al, 2021 ). Cetuximab is a kind of epidermal growth factor receptor (EGFR) inhibitor ( Akimoto et al, 1999 ; Bianco et al, 2000 ; Huang and Harari, 2000 ; Milas et al, 2000 ).…”

Section: Discussionmentioning

confidence: 99%

Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer

et al. 2022

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Background: Given the high incidence and high mortality of cervical cancer (CC) among women in developing countries, identifying reliable biomarkers for the prediction of prognosis and therapeutic response is crucial. We constructed a prognostic signature of cuproptosis-related long non-coding RNAs (lncRNAs) as a reference for individualized clinical treatment.Methods: A total of seven cuproptosis-related lncRNAs closely related to the prognosis of patients with CC were identified and used to construct a prognostic signature via least absolute shrinkage and selection operator regression analysis in the training set. The predictive performance of the signature was evaluated by Kaplan–Meier (K-M) analysis, receiver operating characteristic (ROC) analysis, and univariate and multivariate Cox analyses. Functional enrichment analysis and single-sample gene set enrichment analysis were conducted to explore the potential mechanisms of the prognostic signature, and a lncRNA–microRNA–mRNA network was created to investigate the underlying regulatory relationships between lncRNAs and cuproptosis in CC. The associations between the prognostic signature and response to immunotherapy and targeted therapy were also assessed. Finally, the prognostic value of the signature was validated using the CC tissues with clinical information in my own center.Results: A prognostic signature was developed based on seven cuproptosis-related lncRNAs, including five protective factors (AL441992.1, LINC01305, AL354833.2, CNNM3-DT, and SCAT2) and two risk factors (AL354733.3 and AC009902.2). The ROC curves confirmed the superior predictive performance of the signature compared with conventional clinicopathological characteristics in CC. The ion transport-related molecular function and various immune-related biological processes differed significantly between the two risk groups according to functional enrichment analysis. Furthermore, we discovered that individuals in the high-risk group were more likely to respond to immunotherapy and targeted therapies including trametinib and cetuximab than those in the low-risk group. Finally, CC tissues with clinical data from my own center further verify the robustness of the seven-lncRNA risk signature.Conclusion: We generated a cuproptosis-related lncRNA risk signature that could be used to predict prognosis of CC patients. Moreover, the signature could be used to predict response to immunotherapy and chemotherapy and thus could assist clinicians in making personalized treatment plans for CC patients.

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“…Previous studies have found that PI3K/Akt signaling pathway is activated in a wide range of tumors, the activated PI3K/Akt is associated with progression, invasion, metastasis in multiple tumor types [24]. Akt activation is associated with radioresistance in some malignant tumors such as head and neck cancer, prostate cancers, non-small cell lung cancer and cervical cancer [25][26][27][28]. Mechanistically, PI3K-Akt induces radioresistance by enhancing aerobic glycolysis, accelerating repair of IR-induced DNA double-strand breaks (DNADSB), activating tumor-cell proliferation and attenuating radiation-induced apoptosis [27,29,30].…”

Section: Discussionmentioning

confidence: 99%

IL-11 mediates the Radioresistance of Cervical Cancer Cells via the PI3K/Akt Signaling Pathway

et al. 2021

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Cervical cancer is one of the most common malignant tumors in the female reproductive system. Radioresistance remains a significant factor that limits the efficacy of radiotherapy for cervical cancer. Interleukin‐11 (IL-11) has been reported to be upregulated in various types of human cancer and correlate with clinical stage and poor survival. However, the exact effects and mechanisms of IL-11 in the radioresistance of cervical cancer have not yet been defined. In this research, TCGA databases revealed that IL-11 expression was upregulated in cervical cancer tissues and was associated with clinical stages and poor prognosis in cervical cancer patients. We discovered that IL-11 concentration was significantly upregulated in radioresistant cervical cancer cells. Knocking down IL-11 in Hela cells could reduce clonogenic survival rate, decrease cell viability, induce G2/M phase block, and facilitate cell apoptosis. In contrast, Exogeneous IL-11 in C33A cells could upregulate clonogenic survival rate, increase cell viability, curb G2/M phase block, and cell apoptosis. Mechanistic investigations showed that radioresistance conferred by IL-11 was attributed to the activation of the PI3K/Akt signaling pathway. Altogether, our results demonstrate that IL-11 might be involved in radioresistance, and IL-11 may be a potent radiosensitization target for cervical cancer therapy.

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HPV-induced Nurr1 promotes cancer aggressiveness, self-renewal, and radioresistance via ERK and AKT signaling in cervical cancer

Cited by 18 publications

References 56 publications

Inhibition of TRIM32 by ibr‐7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway

Inhibition of TRIM32 by ibr‐7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway

Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer

IL-11 mediates the Radioresistance of Cervical Cancer Cells via the PI3K/Akt Signaling Pathway

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