Matrix stiffness promotes glioma cell stemness by activating BCL9L/Wnt/β-catenin signaling

Tao, Bei; Song, Yi; Yang, Xiaobo; Peng, Tangming; Peng, Lilei; Xia, Kaiguo; Xia, Xiangguo; Chen, Ligang; Zhong, Chuanhong

doi:10.18632/aging.202449

Cited by 32 publications

(31 citation statements)

References 46 publications

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“…Using U373-MG glioma cells in transwell invasion assay and time-lapse microscopy, the authors show that the migration speed and invasion properties of these cells in the presence of CD44/HA improves with increasing stiffness of the HA hydrogel in which they are cultured (77). Integrin-mediated interaction between glioma cells and microenvironment components such as the glycocalyx or BCL9L have also been described and shown to enhance glioma stemness (75,78,79). Notably, in these studies, glioma stemness also incorporates the treatment-resistant quality of this phenotype and the authors show treatment sensitization employing gain-or loss-of-function methodologies to disturb the specific integrin-mediated mechanosensation (78,79).…”

Section: Influence Of Microenvironmental Tissue Mechanics On Glioma Malignancymentioning

confidence: 98%

“…Integrin-mediated interaction between glioma cells and microenvironment components such as the glycocalyx or BCL9L have also been described and shown to enhance glioma stemness (75,78,79). Notably, in these studies, glioma stemness also incorporates the treatment-resistant quality of this phenotype and the authors show treatment sensitization employing gain-or loss-of-function methodologies to disturb the specific integrin-mediated mechanosensation (78,79). Barnes et al specifically examine recurrent GBM and determine that a bulky glycocalyx in the tumor microenvironment, that is frequently seen in recurrent GBM, interacts with integrins with mechanoreciprocity whereby downstream signaling enhances stemness of the cell which in turn effects increased tension in the glycocalyx to form a feedback loop (79).…”

Section: Influence Of Microenvironmental Tissue Mechanics On Glioma Malignancymentioning

confidence: 99%

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Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities

et al. 2022

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Gliomas represent the most common malignant primary brain tumors, and a high-grade subset of these tumors including glioblastoma are particularly refractory to current standard-of-care therapies including maximal surgical resection and chemoradiation. The prognosis of patients with these tumors continues to be poor with existing treatments and understanding treatment failure is required. The dynamic interplay between the tumor and its microenvironment has been increasingly recognized as a key mechanism by which cellular adaptation, tumor heterogeneity, and treatment resistance develops. Beyond ongoing lines of investigation into the peritumoral cellular milieu and microenvironmental architecture, recent studies have identified the growing role of mechanical properties of the microenvironment. Elucidating the impact of these biophysical factors on disease heterogeneity is crucial for designing durable therapies and may offer novel approaches for intervention and disease monitoring. Specifically, pharmacologic targeting of mechanical signal transduction substrates such as specific ion channels that have been implicated in glioma progression or the development of agents that alter the mechanical properties of the microenvironment to halt disease progression have the potential to be promising treatment strategies based on early studies. Similarly, the development of technology to measure mechanical properties of the microenvironment in vitro and in vivo and simulate these properties in bioengineered models may facilitate the use of mechanical properties as diagnostic or prognostic biomarkers that can guide treatment. Here, we review current perspectives on the influence of mechanical properties in glioma with a focus on biophysical features of tumor-adjacent tissue, the role of fluid mechanics, and mechanisms of mechanical signal transduction. We highlight the implications of recent discoveries for novel diagnostics, therapeutic targets, and accurate preclinical modeling of glioma.

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Section: Influence Of Microenvironmental Tissue Mechanics On Glioma Malignancymentioning

confidence: 98%

Section: Influence Of Microenvironmental Tissue Mechanics On Glioma Malignancymentioning

confidence: 99%

Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities

et al. 2022

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“…A fundamental function of activated fibroblast is its participation in ECM homeostasis by synthesizing ECM constituents, including collagen and fibronectin, and producing ECM-degrading proteases to aid communication and trafficking of inflammatory cells ( Kalluri, 2016 ). While the impact of matrix stiffness remains controversial as studies indicate both softer matrix ( Tan et al, 2014 ; Ng et al, 2021 ) and stiffer matrix ( Pang et al, 2016 ; Tao et al, 2021 ) can instigate cancer stemness, the role of CAF in mediating the stiffness of the ECM illustrates its ability to affect stemness. Indeed, collagen deposited by CAF functions as a mechano signal to escalate stem cell markers and spheroid formation ability ( Cazet et al, 2018 ).…”

Section: Cancer-associated Fibroblast As a Dynamic Player In Promoting Cancer Stemnessmentioning

confidence: 99%

The Role of Cancer-Associated Fibroblast as a Dynamic Player in Mediating Cancer Stemness in the Tumor Microenvironment

Loh

2021

Front. Cell Dev. Biol.

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The enrichment of cancer-associated fibroblast (CAFs) in a tumor microenvironment (TME) cultivates a pro-tumorigenic niche via aberrant paracrine signaling and matrix remodeling. A favorable niche is critical to the maintenance of cancer stem cells (CSCs), a population of cells that are characterized by their enhanced ability to self-renew, metastasis, and develop therapy resistance. Mounting evidence illustrates the interplay between CAF and cancer cells expedites malignant progression. Therefore, targeting the key cellular components and factors in the niche may promote a more efficacious treatment. In this study, we discuss how CAF orchestrates a niche that enhances CSC features and the potential therapeutic implication.

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“…A large number of studies have suggested that WNT signaling is aberrantly activated in GBM and that it promotes GBM growth and invasion via the maintenance of stem cell properties [9][10][11][12][13]. The nuclear accumulation of β-catenin is responsible for the malignant progression and β-catenin protein levels are correlated with malignancy and with the gene expression of cyclin D1 and c-Myc [98][99][100].…”

Section: Canonical Wnt/β-catenin Pathway In Gliomamentioning

confidence: 99%

“…In parallel, a large number of studies have suggested that WNT signaling is aberrantly activated in GBM and that it promotes GBM growth and invasion [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Opposed Interplay between IDH1 Mutations and the WNT/β-Catenin Pathway: Added Information for Glioma Classification

Vallée

Lecarpentier²,

Vallée

2021

Biomedicines

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Gliomas are the main common primary intraparenchymal brain tumor in the central nervous system (CNS), with approximately 7% of the death caused by cancers. In the WHO 2016 classification, molecular dysregulations are part of the definition of particular brain tumor entities for the first time. Nevertheless, the underlying molecular mechanisms remain unclear. Several studies have shown that 75% to 80% of secondary glioblastoma (GBM) showed IDH1 mutations, whereas only 5% of primary GBM have IDH1 mutations. IDH1 mutations lead to better overall survival in gliomas patients. IDH1 mutations are associated with lower stimulation of the HIF-1α a, aerobic glycolysis and angiogenesis. The stimulation of HIF-1α and the process of angiogenesis appears to be activated only when hypoxia occurs in IDH1-mutated gliomas. In contrast, the observed upregula aggressiveness and angiogenesis. Molecular pathways of the malignancy process are involved in early stages of WNT/β-catenin pathway-activated-gliomas, and this even under normoxic conditions. IDH1 mutations lead to decreased activity of the WNT/β-catenin pathway and its enzymatic targets. The opposed interplay between IDH1 mutations and the canonical WNT/β-catenin pathway in gliomas could participate in better understanding of the observed evolution of different tumors and could reinforce the glioma classification.

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Matrix stiffness promotes glioma cell stemness by activating BCL9L/Wnt/β-catenin signaling

Cited by 32 publications

References 46 publications

Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities

Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities

The Role of Cancer-Associated Fibroblast as a Dynamic Player in Mediating Cancer Stemness in the Tumor Microenvironment

Opposed Interplay between IDH1 Mutations and the WNT/β-Catenin Pathway: Added Information for Glioma Classification

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