Gap junction intercellular communication propagates cell death in cancerous cells

Krutovskikh, Vladimir; Piccoli, C.; Yamasaki, Hideo

doi:10.1038/sj.onc.1205187

Cited by 183 publications

(147 citation statements)

References 32 publications

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“…In addition, this paper demonstrates that: (1) There is a gradual reduction of gap junctions as the cells are getting age; comparing with young cells, the middle-aged show less gap junction activity while in senescent cells the gap junction activity is the lowest (Fig 5); (2) A similar reduction in gap junctions is also seen in human fibroblasts undergoing a cisplatin-induced premature senescent changes; (3) Cisplatin-treatment of chicken fibroblasts also induces some premature senescent phenotypes as well as the loss of the membranous Cx43. Promising roles of gap junctions in the controling of cell death have been suggested by reports from others, though different kinds of experiments have led to different conclusions [24][25][26][27]. It is necessary to design further experiments to resolve this mechenism.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

2004

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To examine the role of gap junctions in cell senescence, the changes of gap junctions in cisplatin-induced premature senescence of primary cultured fibroblasts were studied and compared with the replicative senescent human fibroblasts. Dye transfer assay for gap junction function and immunofluorescent staining for connexin 43 protein distribution were done respectively. Furthermore, cytofluorimetry and DAPI fluorescence staining were performed for cell cycle and apoptosis analysis. p53 gene expression level was detected with indirect immunofluorescence. We found that cisplatin (10 mM) treatment could block cell growth cycle at G1 and induced premature senescence. The premature senescence changes included high frequency of apoptosis, elevation of p53 expression, loss of membranous gap junctions and reduction of dye-transfer capacity. These changes were comparable to the changes of replicative senescence of human fibroblasts. It was also concluded that cisplatin could induce premature senescence concomitant with inhibition of gap junctions in the fibroblasts. Loss of functional gap junctions from the cell membrane may account for the reduced intercellular communication in the premature senescent fibroblasts. The cell system we used may provide a model useful for the study of the gap junction thus promoting agents against premature senescence.

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Section: Discussionmentioning

confidence: 99%

Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

2004

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“…Its structural unit is a connexon, and it is a hexameric hemichannel composed of six Cxs (26). GJIC is involved in the growth and differentiation of cells and thus it plays a role in maintaining homeostasis of tissues (27). It is possible that the intercellular exchange of molecules involved in the growth and death of cells may occur through the gap junctions (28).…”

Section: Discussionmentioning

confidence: 99%

Pathological significance of connexin 26 expression in colorectal adenocarcinoma

Ren

Lim²

2008

Oncol Rep

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Abstract. This study was conducted to determine the level of expression and cellular localization of connexin 26 (Cx26) and the expression of p53 in colorectal adenocarcinoma as well as their relationship to clinicopathological features. Immunohistochemical staining was performed in 130 colorectal adenocarcinoma cases. A correlation between the expression levels of the two proteins and an analysis of the clinicopathological features of the samples was performed. There was a statistical significant difference in the Cx26 expression level among normal epithelium (NE), adenomas and adenocarcinomas (p<0.001). Of the 130 adenocarcinomas, 48.5% were positive for Cx26. All of the adenoma and NE samples were positive for Cx26 expression; however, the level of expression of Cx26 in adenomas was smaller than the level of expression for NE. Cytoplasmic staining for Cx26 was observed in the adenocarcinomas (23.8%), but was not observed in the adenoma and NE samples. A positive correlation between a reduction in intercellular Cx26 and tumor invasion was statistically significant (p<0.05). Expression of p53 was positive for 50% of the adenocarcinomas, and the level of p53 was increased in a reverse proportion to the level of Cx26 intercellular staining. In conclusion, loss of intercellular and gain of intracytoplasmic Cx26 expression may play a role in colorectal carcinogenesis and tumor progression.

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“…36 The release of radiation-induced signal factors through GJIC was also suggested by other investigators. 20 Three-dimensional spheroid cultures are more sensitive to ionizing radiation than cell monolayers but that inhibition of GJIC can reverse the effects of contact.…”

Section: Discussionmentioning

confidence: 90%

“…Potential candidates are small molecules including iodide, Ca 2 þ , ROS, or other indeterminate signal factors. 10,11,20,32,36 The prognosis for NSCLC patients remains poor, with a high percentage of patients presenting with advanced disease and metastases. Thus, the therapeutic goal is to provide optimal local control and to eradicate any metastases.…”

Section: Discussionmentioning

confidence: 99%

Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation

et al. 2005

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While external ionizing radiation has been used for treating non-small cell lung cancer (NSCLC), improved efficacy of this modality would be an important advance. Ectopic expression of the sodium iodide symporter (NIS) and thyroperoxidase (TPO) genes in NSCLC cells facilitated concentration of iodide in NSCLC cells, which markedly induced apoptosis in vitro and in vivo. Preincubation of the NIS/TPO-modified NSCLC cells in iodide followed by ionizing radiation generates bystander tumoricidal effects and potently enhances tumor cell killing. This iodide-induced bystander effect is associated with enhanced gap junction intercellular communication (GJIC) activity and increased connexin-43 (Cx43) expression. Thus, iodide may serve as an enhancer to markedly improve the efficacy of radiation therapy in combined therapeutic modalities.

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Gap junction intercellular communication propagates cell death in cancerous cells

Cited by 183 publications

References 32 publications

Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

Pathological significance of connexin 26 expression in colorectal adenocarcinoma

Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation

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