Akt and β-catenin contribute to TMZ resistance and EMT of MGMT negative malignant glioma cell line

Yi, Guozhong; Liu, Yawei; Xiang, Wei; Wang, Hai; Chen, Ziyang; Xie, Sidi; Qi, Songtao

doi:10.1016/j.jns.2016.05.054

Cited by 60 publications

(56 citation statements)

References 32 publications

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“…Epithelial-mesenchymal transition (EMT) is one of the processes involved in GBM dissemination and chemo-resistance [48, 49]. Interestingly, several studies highlighted that the same molecular players that play a key role in EMT of epithelial tumors are also involved in the regulation of motility of non-epithelial tumors, such as GBM [50, 51].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Impairs Glioma Stem Cells Proliferation and Motility by Modulating the Wnt Signaling Pathway

et al. 2017

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Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12–15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be the real driving force of tumor initiation, progression and relapse. Therefore, better therapeutic strategies GSCs-targeted are needed. Resveratrol is a polyphenolic phytoalexin found in fruits and vegetables displaying pleiotropic health benefits. Many studies have highlighted its chemo-preventive and chemotherapeutic activities in a wide range of solid tumors. In this work, we analyzed the effects of Resveratrol exposure on cell viability, proliferation and motility in seven GSC lines isolated from GBM patients. For the first time in our knowledge, we investigated Resveratrol impact on Wnt signaling pathway in GSCs, evaluating the expression of seven Wnt signaling pathway-related genes and the protein levels of c-Myc and β-catenin. Finally, we analyzed Twist1 and Snail1 protein levels, two pivotal activators of epithelial-mesenchymal transition (EMT) program.Results showed that although response to Resveratrol exposure was highly heterogeneous among GSC lines, generally it was able to inhibit cell proliferation, increase cell mortality, and strongly decrease cell motility, modulating the Wnt signaling pathway and the EMT activators. Treatment with Resveratrol may represent a new interesting therapeutic approach, in order to affect GSCs proliferation and motility, even if further investigations are needed to deeply understand the GSCs heterogeneous response.

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Section: Discussionmentioning

confidence: 99%

Resveratrol Impairs Glioma Stem Cells Proliferation and Motility by Modulating the Wnt Signaling Pathway

et al. 2017

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“…β-catenin level also controls tumor differentiation and regulates both MAPK/Erk and PI3K/Akt signaling. In fact, activation of Wnt/β-catenin and AKT pathways mediates chemo-resistance and increased invasion in melanoma cell lines [42]. …”

Section: Wnt/β-catenin Pathway Involvement In Several Malignanciesmentioning

confidence: 99%

Wnt/beta-catenin pathway: modulating anticancer immune response

et al. 2017

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Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. The Wnt pathway mediates biological processes by a canonical or noncanonical pathway, depending on the involvement of β-catenin in signal transduction. β-catenin is a core component of the cadherin protein complex, whose stabilization is essential for the activation of Wnt/β-catenin signaling. As multiple aberrations in this pathway occur in numerous cancers, WNT-directed therapy represents an area of significant developmental therapeutics focus. The recently described role of Wnt/β-catenin pathway in regulating immune cell infiltration of the tumor microenvironment renewed the interest, given its potential impact on responses to immunotherapy treatments. This article summarizes the role of Wnt/β-catenin pathway in cancer and ongoing therapeutic strategies involving this pathway.

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“…Moreover, according to the results of RT-qPCR, western blotting and immunofluorescence staining, the addition of BYHWT significantly increased E-cadherin, as well as reduced Col I and Vimentin. EMT and collagen accumulation is activated by TGF-β1, characterized by the loss of epithelial characteristics (E-cadherin), the acquisition of a mesenchymal phenotype (Vimentin) and the increase of Col I [9]. Therefore, our results indicated that BYHWT can suppress TGF-β1 mediated EMT and TGF-β1 induced collagen deposition in PF.…”

Section: Discussionmentioning

confidence: 55%

“…In addition to direct production of myofibroblasts, EMT can also indirectly create a profibrotic microenvironment by releasing cytokines [8]. As a result, the epithelial cell phenotype such as E-cadherin was lost and transformed into a mesenchymal cell phenotype such as Vimentin [9]. This stimulates alveolar EMT in AECs and transdifferentiation of resting fibroblasts to myofibroblasts, which leads to excessive production of fibrous collagen [10].…”

Section: Introductionmentioning

confidence: 99%

Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-β1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro

Yin

Wei

Wang

et al. 2020

BMC Complement Med Ther

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Background: Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. Buyang Huanwu Tang (BYHWT), a classical traditional Chinese medicine formula, has been widely utilized for the treatment of PF in China. This present study aimed to explore the mechanism of BYHWT in the treatment of PF in vitro. Methods: TGF-β1 stimulated human alveolar epithelial A549 cells were used as in vitro model for PF. Post the treatment of BYHWT, cell viability was measured by MTT assay, and cell morphology was observed under microscope. The epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, Vimentin) and collagen I (Col I) were detected by western blot, immunofluorescence staining and real-time quantitative polymerase chain reaction. With the co-administration of activators (IGF-1, SC79) and inhibitors (LY294002, MK2206), the effect of BYHWT on PI3K/Akt pathway was analyzed by western blot. Results: BYHWT inhibited cell growth, and prevented cell morphology changed from epithelial to fibroblasts in TGF-β1 induced A549 cells. BYHWT decreased Vimentin and Col I, while increased E-cadherin at both protein and mRNA levels. Moreover, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) were significantly down-regulated by BYHWT in TGF-β1 stimulated A549 cells. Conclusion:These results indicate that BYHWT suppressed TGF-β1-induced collagen accumulation and EMT of A549 cells by inhibiting the PI3K/Akt signaling pathway. These findings suggest that BYHWT may have potential for the treatment of PF.

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Akt and β-catenin contribute to TMZ resistance and EMT of MGMT negative malignant glioma cell line

Cited by 60 publications

References 32 publications

Resveratrol Impairs Glioma Stem Cells Proliferation and Motility by Modulating the Wnt Signaling Pathway

Resveratrol Impairs Glioma Stem Cells Proliferation and Motility by Modulating the Wnt Signaling Pathway

Wnt/beta-catenin pathway: modulating anticancer immune response

Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-β1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro

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