Connexin and pannexin channels in cancer

Jiang, Jean X.; Peñuela, Silvia

doi:10.1186/s12860-016-0094-8

Cited by 56 publications

(61 citation statements)

References 191 publications

(234 reference statements)

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“…In addition, the possible involvement of pannexin channels also cannot be ignored (Panchin et al, 2000). Multiple studies suggest that these two types of hemichannels have a close relationship and work coordinately in the CNS that differentially regulates the ionic and metabolic fluxes and cellular function (Decrock et al, 2015; Jiang and Penuela, 2016). …”

Section: Connexin Hemichannelsmentioning

confidence: 99%

Connexin channel and its role in diabetic retinopathy

Roy

Jiang

et al. 2017

Progress in Retinal and Eye Research

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Diabetic retinopathy is the leading cause of blindness in the working age population. Unfortunately, there is no cure for this devastating ocular complication. The early stage of diabetic retinopathy is characterized by the loss of various cell types in the retina, namely endothelial cells and pericytes. As the disease progresses, vascular leakage, a clinical hallmark of diabetic retinopathy, becomes evident and may eventually lead to diabetic macular edema, the most common cause of vision loss in diabetic retinopathy. Substantial evidence indicates that the disruption of connexin-mediated cellular communication plays a critical role in the pathogenesis of diabetic retinopathy. Yet, it is unclear how altered communication via connexin channel mediated cell-to-cell and cell-to-extracellular microenvironment is linked to the development of diabetic retinopathy. Recent observations suggest the possibility that connexin hemichannels may play a role in the pathogenesis of diabetic retinopathy by allowing communication between cells and the microenvironment. Interestingly, recent studies suggest that connexin channels may be involved in regulating retinal vascular permeability. These cellular events are coordinated at least in part via connexin-mediated intercellular communication and the maintenance of retinal vascular homeostasis. This review highlights the effect of high glucose and diabetic condition on connexin channels and their impact on the development of diabetic retinopathy.

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Section: Connexin Hemichannelsmentioning

confidence: 99%

Connexin channel and its role in diabetic retinopathy

Roy

Jiang

et al. 2017

Progress in Retinal and Eye Research

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“…Concerning a possible use of CBX in cancer, it has been shown that CBX inhibits the expression of the apoptosis-inhibitor-protein BIRC5/survivin and thereby triggers apoptosis in K562 leukemic cells [46] and enhances TRAIL-induced apoptosis in human glioma [47]. Regarding its function as a gap junction inhibitor, particularly as a [48].…”

Section: Discussionmentioning

confidence: 99%

A drug library screen identifies Carbenoxolone as novel FOXO inhibitor that overcomes FOXO3-mediated chemoprotection in high-stage neuroblastoma

et al. 2019

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The transcription factor FOXO3 has been associated in different tumor entities with hallmarks of cancer, including metastasis, tumor angiogenesis, maintenance of tumor-initiating stem cells, and drug resistance. In neuroblastoma (NB), we recently demonstrated that nuclear FOXO3 promotes tumor angiogenesis in vivo and chemoresistance in vitro. Hence, inhibiting the transcriptional activity of FOXO3 is a promising therapeutic strategy. However, as no FOXO3 inhibitor is clinically available to date, we used a medium-throughput fluorescence polarization assay (FPA) screening in a drugrepositioning approach to identify compounds that bind to the FOXO3-DNA-binding-domain (DBD). Carbenoxolone (CBX), a glycyrrhetinic acid derivative, was identified as a potential FOXO3-inhibitory compound that binds to the FOXO3-DBD with a binding affinity of 19 µM. Specific interaction of CBX with the FOXO3-DBD was validated by fluorescencebased electrophoretic mobility shift assay (FAM-EMSA). CBX inhibits the transcriptional activity of FOXO3 target genes, as determined by chromatin immunoprecipitation (ChIP), DEPP-, and BIM promoter reporter assays, and real-time RT-PCR analyses. In high-stage NB cells with functional TP53, FOXO3 triggers the expression of SESN3, which increases chemoprotection and cell survival. Importantly, FOXO3 inhibition by CBX treatment at pharmacologically relevant concentrations efficiently repressed FOXO3-mediated SESN3 expression and clonogenic survival and sensitized high-stage NB cells to chemotherapy in a 2D and 3D culture model. Thus, CBX might be a promising novel candidate for the treatment of therapy-resistant high-stage NB and other "FOXO-resistant" cancers.

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“…Transmembrane proteins, form channels for the release of ATP and other metabolites [210]. Auto-and paracrine cell-cell communication…”

Section: Cell-to-cell Communicationmentioning

confidence: 99%

Modifying the Tumour Microenvironment: Challenges and Future Perspectives for Anticancer Plasma Treatments

Privat-Maldonado

Bengtson

Razzokov

et al. 2019

Cancers

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Tumours are complex systems formed by cellular (malignant, immune, and endothelial cells, fibroblasts) and acellular components (extracellular matrix (ECM) constituents and secreted factors). A close interplay between these factors, collectively called the tumour microenvironment, is required to respond appropriately to external cues and to determine the treatment outcome. Cold plasma (here referred as ‘plasma’) is an emerging anticancer technology that generates a unique cocktail of reactive oxygen and nitrogen species to eliminate cancerous cells via multiple mechanisms of action. While plasma is currently regarded as a local therapy, it can also modulate the mechanisms of cell-to-cell and cell-to-ECM communication, which could facilitate the propagation of its effect in tissue and distant sites. However, it is still largely unknown how the physical interactions occurring between cells and/or the ECM in the tumour microenvironment affect the plasma therapy outcome. In this review, we discuss the effect of plasma on cell-to-cell and cell-to-ECM communication in the context of the tumour microenvironment and suggest new avenues of research to advance our knowledge in the field. Furthermore, we revise the relevant state-of-the-art in three-dimensional in vitro models that could be used to analyse cell-to-cell and cell-to-ECM communication and further strengthen our understanding of the effect of plasma in solid tumours.

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Connexin and pannexin channels in cancer

Cited by 56 publications

References 191 publications

Connexin channel and its role in diabetic retinopathy

Connexin channel and its role in diabetic retinopathy

A drug library screen identifies Carbenoxolone as novel FOXO inhibitor that overcomes FOXO3-mediated chemoprotection in high-stage neuroblastoma

Modifying the Tumour Microenvironment: Challenges and Future Perspectives for Anticancer Plasma Treatments

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