Migration Phenotype of Brain-Cancer Cells Predicts Patient Outcomes

Smith, Chris; Kilic, Onur; Schiapparelli, Paula; Guerrero-Cázares, Hugo; Kim, Deok Ho; Sedora‐Roman, Neda I.; Gupta, Saksham; O'Donnell, Thomas J.; Chaichana, Kaisorn L.; Rodríguez, Fausto J.; Abbadi, Sara; Park, Jin Seok; Quiñones‐Hinojosa, Alfredo; Levchenko, Andre

doi:10.1016/j.celrep.2016.05.042

Cited by 66 publications

(67 citation statements)

References 36 publications

(56 reference statements)

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“…PTEN L320S -GFP, PTEN T277A -GFP, and PTEN delEx3 -GFP showed decreased activity to suppress cell migration, as measured by the Transwell (Fig. 1K) or 3-D nanopattern migration assays 2, 41, 42 (Fig. 1L).…”

Section: Resultsmentioning

confidence: 96%

Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization

et al. 2017

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PTEN is a PIP3 phosphatase that antagonizes oncogenic PI3-kinase signalling. Due to its critical role in suppressing the potent signalling pathway, it is one of the most mutated tumour suppressors, especially in brain tumours. It is generally thought that PTEN deficiencies predominantly result from either loss of expression or enzymatic activity. By analysing PTEN in malignant glioblastoma primary cells derived from 16 of our patients, we report mutations that block localization of PTEN at the plasma membrane and nucleus without affecting lipid phosphatase activity. Cellular and biochemical analyses as well as structural modelling revealed that two mutations disrupt intramolecular interaction of PTEN and open its conformation, enhancing polyubiquitination of PTEN and decreasing protein stability. Moreover, promoting mono-ubiquitination increases protein stability and nuclear localization of mutant PTEN. Thus, our findings provide a molecular mechanism for cancer-associated PTEN defects and may lead to a brain cancer treatment that targets PTEN mono-ubiquitination.

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Section: Resultsmentioning

confidence: 96%

Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization

et al. 2017

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“…[3][4][5] Emerging experimental and histological evidence indicates that GBM cell migration is accompanied by the expression of stem cell markers and can be predictive of patient outcomes. [6][7][8] Therefore, interventions that specifically target the invasive GBM phenotype are highly desirable. However, the molecular mechanisms underlying the infiltrative nature of GBM cells are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Glioblastoma Spheroid Infiltration of Early-Stage Cerebral Organoids Models Brain Tumor Invasion

et al. 2018

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Organoid methodology provides a platform for the ex vivo investigation of the cellular and molecular mechanisms underlying brain development and disease. High-grade brain tumor glioblastoma multiforme (GBM) is considered a cancer of unmet clinical need, in part due to GBM cell infiltration into healthy brain parenchyma making complete surgical resection improbable. Modelling the process of GBM invasion in real time is challenging as it requires both tumor and neural tissue compartments. Here, we demonstrate that human GBM spheroids possess the ability to spontaneously infiltrate earlystage cerebral organoids (eCO). The resulting formation of hybrid organoids demonstrated an invasive tumor phenotype that was distinct from non-cancerous adult neural progenitor (NP) spheroid incorporation into eCOs. These findings provide a basis for the modelling and quantification of the GBM infiltration process using a stem cell-based organoid approach, and may be used for the identification of anti-GBM invasion strategies.

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“…CCV can persist over several division times – up to 48 hours in human cells [111]. CCV in motility properties may be particularly important in studying three-dimensional motility and motility in vivo [115, 116]. For instance, presence of a subset of cells with a large motile response to PDGF predicts patient outcomes in glioblastoma [116].…”

Section: Fundamental Bounds: What Is the Best Estimate A Cluster Canmentioning

confidence: 99%

Collective gradient sensing and chemotaxis: modeling and recent developments

Camley

2018

J. Phys.: Condens. Matter

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Cells measure a vast variety of signals, from their environment’s stiffness to chemical concentrations and gradients; physical principles strongly limit how accurately they can do this. However, when many cells work together, they can cooperate to exceed the accuracy of any single cell. In this Topical Review, I will discuss the experimental evidence showing that cells collectively sense gradients of many signal types, and the models and physical principles involved. I also propose new routes by which experiments and theory can expand our understanding of these problems.

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Migration Phenotype of Brain-Cancer Cells Predicts Patient Outcomes

Cited by 66 publications

References 36 publications

Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization

Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization

Spontaneous Glioblastoma Spheroid Infiltration of Early-Stage Cerebral Organoids Models Brain Tumor Invasion

Collective gradient sensing and chemotaxis: modeling and recent developments

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