Signaling Determinants of Glioma Cell Invasion

Kwiatkowska, Aneta; Symons, Marc

doi:10.1007/978-3-030-30651-9_7

Cited by 81 publications

(24 citation statements)

References 188 publications

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“…High-grade gliomas, such as glioblastoma (GBM) and anaplastic astrocytoma, cause human mortality both in children and adults 3 , 4 . Dysregulation of multiple signaling cascades and complex signaling crosstalk are vital in the tumorigenesis and progression of human glioma 5 - 9 . These cascades include phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) 10 , p53, retinoblastoma (Rb), epidermal growth factor receptor (EGFR) and Wnt/β-catenin 11 as well as signal transducer and activator of transcription (STAT), neurotrophic tyrosine receptor kinase (NTRK), fibroblast growth factor receptor (FGFR) and many others 5 , 6 .…”

Section: Introductionmentioning

confidence: 99%

Neuronal-driven glioma growth requires Gαi1 and Gαi3

Yin¹,

Liu²,

Chen³

et al. 2021

Theranostics

113

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Neuroligin-3 (NLGN3) is necessary and sufficient to promote glioma cell growth. The recruitment of Gαi1/3 to the ligand-activated receptor tyrosine kinases (RTKs) is essential for mediating oncogenic signaling. Methods: Various genetic strategies were utilized to examine the requirement of Gαi1/3 in NLGN3-driven glioma cell growth. Results: NLGN3-induced Akt-mTORC1 and Erk activation was inhibited by decreasing Gαi1/3 expression. In contrast ectopic Gαi1/3 overexpression enhanced NLGN3-induced signaling. In glioma cells, NLGN3-induced cell growth, proliferation and migration were attenuated by Gαi1/3 depletion with shRNA, but facilitated with Gαi1/3 overexpression. Significantly, Gαi1/3 silencing inhibited orthotopic growth of patient-derived glioma xenografts in mouse brain, whereas forced Gαi1/3-overexpression in primary glioma xenografts significantly enhanced growth. The growth of brain-metastatic human lung cancer cells in mouse brain was largely inhibited with Gαi1/3 silencing. It was however expedited with ectopic Gαi1/3 overexpression. In human glioma Gαi3 upregulation was detected, correlating with poor prognosis. Conclusion: Gαi1/3 mediation of NLGN3-induced signaling is essential for neuronal-driven glioma growth .

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Section: Introductionmentioning

confidence: 99%

Neuronal-driven glioma growth requires Gαi1 and Gαi3

Yin¹,

Liu²,

Chen³

et al. 2021

Theranostics

113

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“…The proneural subtype of GBM was characterized by PDGFRA amplification as well as p53 and IDH1 mutations [3]. The protein CD44 is the best known molecule associated with invasion in many tumours, including gliomas [8,9]. Increased expression of CD44 was also found in the mesenchymal subtype of GBMs [3].…”

Section: Introductionmentioning

confidence: 99%

Molecular classification of diffuse gliomas

Jakovlevs¹,

Vanags²,

Gardovskis³

et al. 2019

pjp

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In this study we assessed whether gliomas could be subdivided into different molecular subtypes by immunohistochemistry (IHC) reminiscent of those first described by Verhaak et al. in 2010 (classical, proneural, mesenchymal and neural). We also evaluated the prognostic significance of single molecular factors and searched for significant correlations between markers. In this study, we included 146 patients with glioblastomas (GBMs) and 26 with diffuse astrocytomas (DAs). The glioma samples were tested for PDGFRA, IDH1 R132H, CD44, p53, Ki-67, p21 and p27 expression. We found that gliomas could be subdivided into molecular subtypes by IHC. Fifty per cent of GBMs were of the proneural subtype, 18.5% of mesenchymal subtype and 31.5% were not otherwise classified. However, most of the DAs (92.3%) belonged to the proneural subtype. No prognostic role was found for the molecular subtypes, but predictive roles were noted. Both proneural and mesenchymal molecular subtypes showed a benefit from the addition of chemotherapy and radiotherapy; however, the mesenchymal subtype showed a greater response. Interestingly, the mesenchymal subtype did not receive any benefit from the addition of radiotherapy compared with palliative management and surgery alone. Regarding single molecular markers, only IDH1 R132H was found to have a prognostic role for GBMs. There was a trend towards better survival in tumours with lower PDGFRA expression (p = 0.066). In DAs, PDGFRA and Ki-67 expression had prognostic roles. The following statistically significant correlations were found in GBMs: Ki-67/p53, Ki-67/p27 and p53/PDGFRA; in DAs: p53/ PDGFRA, CD44/PDGFRA, and p21/PDGFRA.

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“…Integrin-mediated signaling activates transcription factors, which culminate in the secretion of proteolytic enzymes, such as urokinasetype plasminogen activator (uPA), a disintegrin and metalloproteinase (ADAM), and MMPs that cleave cell surface adhesion molecules, including CD44 and L1CAM (L1 cell adhesion molecule ;Kwiatkowska & Symons, 2013). The integrin avb8 is also described as a major driver of cell invasion in glioblastoma multiforme (Reyes et al, 2013).…”

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confidence: 99%

Glioma infiltration and extracellular matrix: key players and modulators

Ferrer

Moura‐Neto

Mentlein

2018

Glia

155

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An outstanding characteristic of gliomas is their infiltration into brain parenchyma, a property that impairs complete surgical resection; consequently, these tumors might recur, resulting in a high mortality rate. Gliomas invade along preferential routes, such as those along white matter tracts and in the perineuronal and perivascular spaces. Brain extracellular components and their partners and modulators play a crucial role in glioma cell invasion. This review presents an extensive survey of the literature, showing how the brain extracellular matrix (ECM) is modulated during the glioma infiltration process. We explore aspects of ECM interaction with glioma cells, reviewing the main glycosaminoglycans, glycoproteins and proteoglycans. We discuss the roles of ECM-binding proteins, including CD44, RHAMM, integrins and axonal guidance molecules, and highlight the role of proteases and glycosidases in glioma infiltration; in binding and release chemokines, cytokines and growth factors; and in generating new bioactive ECM fragments. We also consider the roles of cytoskeletal signaling, angiogenesis, miRNAs and the glial-to-mesenchymal transition linked to glioma invasion. We closely discuss therapeutic approaches based on the modulation of the extracellular matrix, targeting the control of glioma infiltration, its relative failure in clinical trials, and potential means to overcome this difficulty.

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Signaling Determinants of Glioma Cell Invasion

Cited by 81 publications

References 188 publications

Neuronal-driven glioma growth requires Gαi1 and Gαi3

Neuronal-driven glioma growth requires Gαi1 and Gαi3

Molecular classification of diffuse gliomas

Glioma infiltration and extracellular matrix: key players and modulators

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