Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer

Lu, Junmi; Zang, Hongjing; Zheng, Hongmei; Zhan, Yuting; Yang, Yang; Zhang, Yuting; Liu, Sile; Feng, Juan; Wen, Qiuyuan; Long, Mengping; Fan, Songqing

doi:10.1371/journal.pone.0227768

Cited by 27 publications

(26 citation statements)

References 41 publications

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“…The mTOR signaling pathway is an important pathway that is activated in multiple pathological processes and is thereby involved in tumor survival, proliferation and distant metastasis [ 16 ]. Deregulation of the mTOR pathway is observed in various cancers [ 17 , 18 ]. It has also been reported that the mTOR pathway regulates angiogenesis by modulating VEGF gene expression [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Antitumor effect and molecular mechanism of fucoidan in NSCLC

Chen

Sun

Wei

et al. 2021

BMC Complement Med Ther

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Background Fucoidan, a water-soluble polysaccharide, exerts anticoagulant and antiviral functions. It was recently reported that fucoidan also exerts an antitumor function. Lung cancer is one of the most common cancers in the world. The aim of this study was to investigate anti-tumor,apoptosis and anti-metastasis effects of fucoidan in both cell-based assays and mouse xenograft model, as well as to clarify possible role of m-TOR pathway in the protection. Methods In vitro: Different concentrations of fucoidan were given to act on non-small cell lung cancer (NSCLC) cell lines A549 and H1650. The effects of fucoidan on cell proliferation were observed by detecting cyclin expression levels, CCK8 and EDU experiments and cloning experiments. The apoptotic level was detected by flow cytometry and the apoptotic protein level was detected by Westernblot. By detecting the expression of adhesion molecules, the expression of matrix metalloproteinase (MMP) family, and Transwell cell invasion and migration experiment, the effect of fucoidan on cell adhesion, invasion and migration was observed. Meanwhile the effect of fucoidan on angiogenesis was observed by detecting the expression of vascular endothelial growth factor (VEGF). In vivo experiment: An animal model of NSCLC cell mouse subcutaneous xenograft tumor was established to analyze the correlation between the consumption of fucoidan and the size and volume of xenograft tumor through gross observation. Through immunohistochemical staining and immunofluorescence double staining, ki67 and cell adhesion molecules (E-cadherin, N-cadherin and CD31) and VEGF-A in the tumor were detected, and the correlation between the amount of fucoidan and the above indexes was analyzed. Results Fucoidan inhibited the proliferation and angiogenesis of NSCLC cells via the mTOR pathway and promoted their apoptosis by increasing the Bax/Bcl-2 ratio. Not only that, fucoidan inhibited NSCLC cell invasion via epithelial–mesenchymal transformation (EMT). The mice fed fucoidan exhibited significant reductions in tumor volumes and weights. These indicators (Ki67, VEGF-A,N-cadherin) were decreased and E-cadherin expression was up-regulated in A549 mice that treated with fucoidan. The results showed that fucoidan inhibited tumor proliferation in vivo by affecting the expression of related proteins. Conclusion Fucoidan conveys antitumor effects and our results represent an ideal therapeutic agent for NSCLC.

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Section: Introductionmentioning

confidence: 99%

Antitumor effect and molecular mechanism of fucoidan in NSCLC

Chen

Sun

Wei

et al. 2021

BMC Complement Med Ther

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“…At the same time, conflicting evidence exists for non-small cell lung cancer (NSCLC). Thus, Lu and colleagues provided evidence for the overexpression of pAKT being associated with metastasis and poor prognosis by processing 341 NSCLC samples [ 32 ]. On the contrary, Shah and co-workers reported on pAKT as a favorable prognostic factor despite being associated with a high tumor grade in the analysis of 82 NSCLC specimens [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of PI3K/mTOR/AKT Pathway Elements to Serve as Biomarkers and Therapeutic Targets in Penile Cancer

Thomas¹,

Reetz²,

Stenzel³

et al. 2021

Cancers

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The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan–Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.

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“…The active form of MNK1, p-MNK1 (Thr197/202), and phosphorylated eIF4E, p-eIF4E, are increased in lung cancer and correlate with poor overall survival of NSCLC patients [131,66]. In addition, high levels of p-MNK1 might act as an independent poor prognostic biomarker for these patients [66].…”

Section: Mnk In Lung Cancermentioning

confidence: 99%

Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer

Pinto-Díez

Ferreras-Martín

Carrión-Marchante

et al. 2020

IJMS

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The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are involved in oncogenic transformation and can promote metastasis and tumor progression. In human cells, there are four MNKs isoforms (MNK1a/b and MNK2a/b), derived from two genes by alternative splicing. These kinases play an important role controlling the expression of specific proteins involved in cell cycle, cell survival and cell motility via eukaryotic initiation factor 4E (eIF4E) regulation, but also through other substrates such as heterogeneous nuclear ribonucleoprotein A1, polypyrimidine tract-binding protein-associated splicing factor and Sprouty 2. In this review, we provide an overview of the role of MNK in human cancers, describing the studies conducted to date to elucidate the mechanism involved in the action of MNKs, as well as the development of MNK inhibitors in different hematological cancers and solid tumors.

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Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer

Abstract: The Akt (protein kinase B)

Cited by 27 publications

References 41 publications

Antitumor effect and molecular mechanism of fucoidan in NSCLC

Antitumor effect and molecular mechanism of fucoidan in NSCLC

Assessment of PI3K/mTOR/AKT Pathway Elements to Serve as Biomarkers and Therapeutic Targets in Penile Cancer

Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer

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