Identification of a novel switch in the dominant forms of cell adhesion-mediated drug resistance in glioblastoma cells

Westhoff, Mike‐Andrew; Zhou, Shaoxia; Bachem, Max G.; Debatin, Klaus‐Michael; Fulda, Simone

doi:10.1038/onc.2008.148

Cited by 57 publications

(67 citation statements)

References 35 publications

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“…CAM-DR represents a promising approach for pharmacological interventions based on the inhibition of integrin-dependent signaling by statin (Schmidmaier et al, 2004), integrin expression by Bortezomib (Noborio-Hatano et al, 2009) or integrin-ECM binding by small molecules such as FNIII14 interfering with attachment to fibronectin (Matsunaga et al, 2008). Finally, it is important to note that, not only cell-tomatrix, but also cell-to-cell interaction may protect cells against drugs, and that gap-junction poisons, such as carbenoxyolone may act as chemosensitizers (Westhoff et al, 2008).…”

Section: Impact Of Anti-cancer Agents On Integrin Expression and Funcmentioning

confidence: 99%

Influence of stress on extracellular matrix and integrin biology

et al. 2011

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Section: Impact Of Anti-cancer Agents On Integrin Expression and Funcmentioning

confidence: 99%

Influence of stress on extracellular matrix and integrin biology

et al. 2011

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“…Failure to establish or maintain adherens junctions is also thought to cause apoptosis (Hermiston and Gordon, 1995;Shen and Kramer, 2004). This particular process is still poorly understood and indeed has been difficult to study because of confounding effects from anoikis and additional signals from the local microenvironment (Shen and Kramer, 2004;Westhoff and Fulda, 2009;Westhoff et al, 2008). Finally, disruption of apicobasal polarity can also trigger apoptosis: in Drosophila embryos, removal of apical determinants, such as Crb, Sdt or Baz, leads to widespread cell death (Abrams et al, 1993;Knust et al, 1993;Muller and Wieschaus, 1996;Tepass et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Apical deficiency triggers JNK-dependent apoptosis in the embryonic epidermis of Drosophila

Kolahgar¹,

Bardet²,

Langton³

et al. 2011

Development

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SUMMARYEpithelial homeostasis and the avoidance of diseases such as cancer require the elimination of defective cells by apoptosis. Here, we investigate how loss of apical determinants triggers apoptosis in the embryonic epidermis of Drosophila. Transcriptional profiling and in situ hybridisation show that JNK signalling is upregulated in mutants lacking Crumbs or other apical determinants. This leads to transcriptional activation of the pro-apoptotic gene reaper and to apoptosis. Suppression of JNK signalling by overexpression of Puckered, a feedback inhibitor of the pathway, prevents reaper upregulation and apoptosis. Moreover, removal of endogenous Puckered leads to ectopic reaper expression. Importantly, disruption of the basolateral domain in the embryonic epidermis does not trigger JNK signalling or apoptosis. We suggest that apical, not basolateral, integrity could be intrinsically required for the survival of epithelial cells. In apically deficient embryos, JNK signalling is activated throughout the epidermis. Yet, in the dorsal region, reaper expression is not activated and cells survive. One characteristic of these surviving cells is that they retain discernible adherens junctions despite the apical deficit. We suggest that junctional integrity could restrain the pro-apoptotic influence of JNK signalling.

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“…Accordingly, improved treatment strategies, such as the use of TRAIL coupled with other conventional or novel drugs for instance temozolomide (TMZ) [10], paclitaxel, carboplatin and bevacizumab [11], phosphoinositide-3-kinase (PI3K)/ mammalian target of rapamycin (mTOR) inhibitor PI-103 [12], Bortezomib [13], or histone deacetylase inhibitor Entinostat [14], have been explored to enhance the therapeutic efficacy mediated by TRAIL. In gliomas, a study has shown that the use of a gap junction (GJ) inhibitor, carbenoxolone (CBX), was capable of enhancing TRAIL, FasL, and etoposide-induced apoptosis through the disruption of cell-cell interaction [15].…”

Section: Introductionmentioning

confidence: 99%

Carbenoxolone Enhances TRAIL-Induced Apoptosis Through the Upregulation of Death Receptor 5 and Inhibition of Gap Junction Intercellular Communication in Human Glioma

Yulyana

Endaya

et al. 2013

Stem Cells and Development

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been used extensively in cancer therapy. However, more than half of glioblastoma multiforme are insensitive to the apoptotic effect of TRAIL. Improvement in therapeutic modalities that enhances the efficacy of TRAIL in glioma is much sought after. In this study, we combined the tumor selectivity of TRAIL and tumor-homing properties of mesenchymal stem cells (MSC) with gap junction (GJ) inhibitory effect of carbenoxolone (CBX) to target orthotopic glioma. MSC were engineered to express TRAIL (MSC-TRAIL) by incorporating the secretable trimeric form of TRAIL into a Herpes Simplex Virus (HSV) type I amplicon vector. Our results showed that combined treatment of MSC-TRAIL and CBX enhanced glioma cell death, especially in three primary human glioma isolates, of which two of those are marginally sensitive to TRAIL. CBX enhanced TRAIL-induced apoptosis through upregulation of death receptor 5, blockade of GJ intercellular communication, and downregulation of connexin 43. Dual arm therapy using TRAIL and CBX prolonged the survival of treated mice by *27% when compared with the controls in an intracranial glioma model. The enhanced efficacy of TRAIL in combination with CBX coupled with the minimal cytotoxic nature of CBX suggested a favorable clinical usage of this treatment regimen.

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Identification of a novel switch in the dominant forms of cell adhesion-mediated drug resistance in glioblastoma cells

Cited by 57 publications

References 35 publications

Influence of stress on extracellular matrix and integrin biology

Influence of stress on extracellular matrix and integrin biology

Apical deficiency triggers JNK-dependent apoptosis in the embryonic epidermis of Drosophila

Carbenoxolone Enhances TRAIL-Induced Apoptosis Through the Upregulation of Death Receptor 5 and Inhibition of Gap Junction Intercellular Communication in Human Glioma

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