Negative growth control of renal cell carcinoma cell by connexin 32: Possible involvement of Her‐2

Fujimoto, Eriko; Satoh, Haruna; Negishi, Etsuko; Ueno, Koichi; Nagashima, Yoji; Hagiwara, Kiyokazu; Yamasaki, Hiroshi; Yano, Tomohiro

doi:10.1002/mc.20025

Cited by 36 publications

(35 citation statements)

References 30 publications

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“…the density attained by cells in culture upon entering the plateau phase [18][19][20], and the inhibition of anchorage-independent growth [21], i.e. the partial reversion of the tumour phenotype represented by a decrease in the proliferation rate of connexin-transfected tumour cells in semi-solid media [16,22,23]. An inverse relationship between connexin expression and tumour cell proliferation has long been regarded as resulting from the synchronising effect of gap junctional coupling on cell physiology.…”

Section: The Involvement Of Gap Junctions In the Regulation Of Tumourmentioning

confidence: 99%

The stage-specific function of gap junctions during tumourigenesis

Czyż

2008

Cellular and Molecular Biology Letters

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Tumour development is a process resulting from the disturbance of various cellular functions including cell proliferation, adhesion and motility. While the role of these cell parameters in tumour promotion and progression has been widely recognized, the mechanisms that influence gap junctional coupling during tumorigenesis remain elusive. Neoplastic cells usually display decreased levels of connexin expression and/or gap junctional coupling. Thus, impaired intercellular communication via gap junctions may facilitate the release of a potentially neoplastic cell from the controlling regime of the surrounding tissue, leading to tumour promotion. However, recent data indicates that metastatic tumour cell lines are often characterized by relatively high levels of connexin expression and gap junctional coupling. This review outlines current knowledge on the role of connexins in tumorigenesis and the possible mechanisms of the interference of gap junctional coupling with the processes of tumour invasion and metastasis. GAP JUNCTIONS -THEIR STRUCTURE AND BASIC FUNCTIONS IN TISSUE HOMEOSTASISGap junctions are aqueous intercellular channels which directly link the cytoplasmic compartments of adjacent cells (Fig. 1). These channels are formed upon the docking of two connexons, hexameric hemichannels built of proteins belonging to the connexin family [1]. Gap junctions are present in almost all vertebrate tissues, where they permit the intercellular exchange of small (< 1 kDa) metabolites and second messengers, and thus synchronise cellular functions in tissues [2][3][4]. Representative examples of the synchronising function of gap junctional coupling in tissues include electrical and metabolic coupling. In the former, gap junctions take part in the intercellular spreading of membrane depolarisation by permitting the rapid cell-to-cell transfer of calcium ions between cardiac muscle cells [1], or by constituting electrical synapses in the nervous system [5]. Metabolic coupling is established when the stimulation of one cell is propagated to a cluster of cells through the spreading of active substances, such as monosaccharides and cyclic nucleotides [2,6]. While electrical coupling predominantly synchronizes cell functions in excitable tissues, metabolic coupling affects the homeostasis of a spectrum of multicellular systems, including both excitable and non-excitable tissues. The crucial role of gap junctions in the regulation of tissue homeostasis is illustrated by the functional impairment of many vertebrate tissues occurring when there is deficient gap junctional communication [7,8]. For instance, disruption of the function of the gene encoding Cx32 is associated with the progressive degeneration of the peripheral nerves, resulting from the impairment of the diffusion of nutrients and signalling molecules between the perinuclear and periaxonal Schwann cell cytoplasm [for review see [9]. Furthermore, abnormalities have been observed in Cx32-deficient mouse livers: Cx32 disruption leads to a decrease in the disc...

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Section: The Involvement Of Gap Junctions In the Regulation Of Tumourmentioning

confidence: 99%

The stage-specific function of gap junctions during tumourigenesis

Czyż

2008

Cellular and Molecular Biology Letters

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“…The sense and anti-sense strands of non-specific control siRNA were: sense: 5 0 -UUCUCCGAACGUGUCACGUdTdT-3 0 ; anti-sense: 5 0 -ACGUGACACGUUCGGAGAAdTdT-3 0 . SiRNA was transfected into A549 cells using RNAiFect Transfection Reagent (Invitrogen) as previously reported [18]. At 12 h after transfection, the cells were incubated for 72 h in culture medium containing 20 lM cPGI 2 or the vehicle, and the IP expression was subsequently determined by RT-PCR.…”

Section: Sirna Design Preparation and Transfectionmentioning

confidence: 99%

Peroxisome proliferator‐activated receptor δ as a molecular target to regulate lung cancer cell growth

et al. 2005

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It has been assumed that prostaglandin (PG)I 2 signaling contributes to the negative growth control of lung cancer cells; however, the mechanism remains unresolved. PGI 2 functions through a cell surface G protein-coupled receptor (prostaglandin I2-binding receptor, IP) and also exerts an effect by interacting with a nuclear hormone receptor, peroxisome proliferator-activated receptor d (PPARd). We found that PPARd was a key molecule of PGI 2 signaling to give negative growth control of lung cancer cells (A549), using carbarprostacyclin, a PGI 2 agonist for IP and PPARd, and L-165041, a PPARd agonist. Furthermore, PPARd-induced cell growth control was reinforced by the inhibition of cyclooxygenase. These results suggest that PPARd activation under the suppression of PG synthesis is important to regulate lung cancer cell growth.

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“…However, the capability of cancer cells to penetrate vascular walls, a crucial stage of cancer invasion depending on cancer cell motility, is a function involving other cell properties, such as the expression of connexins and gap junctional intercellular coupling (GJIC). In particular, deregulation of GJIC facilitates early carcinogenesis and the formation of a local hyperplasia (2)(3)(4)(5). In contrast, restoration of GJIC between cancer and normal cells is crucial for malignant cell dissemination (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Fenofibrate attenuates contact-stimulated cell motility and gap junctional coupling in DU-145 human prostate cancer cell populations

Madeja

2011

Oncol Rep

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Abstract. In the present study, we investigated the effects of fenofibrate on the invasive potential of DU-145 human prostate cancer cells in the context of gap junctional intercellular coupling and the formation of reactive oxygen species. Timelapse analyses of cell motility, accompanied by tests of cell viability, membrane microviscosity, reactive oxygen species accumulation and the function of gap junctional protein connexin 43 were performed in monolayer cultures of DU-145 cells following fenofibrate administration. Fenofibrate inhibited the motility of DU-145 cells and attenuated gap junctional intercellular coupling in a manner independent of its effects on cell viability, PPARα activation and cell membrane microviscosity. Instead, N-acetyl-L-cysteine, a scavenger of reactive oxygen species, restored cell motility and gap junctional coupling in fenofibrate-treated DU-145 cell populations. These data indicate that two parameters crucial for cancer cell metastatic potential, i.e. cell motility and gap junctional coupling, are inhibited by fenofibrate. Thus, fenofibrate affects prostate cancer cell invasion via an orchestrated action on versatile cancer cell properties determining this process. A novel mechanism of anti-invasive activity of fenofibrate, which depends on its interference with cell motility and the function of gap junctions regulated by reactive oxygen species, is suggested.

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Negative growth control of renal cell carcinoma cell by connexin 32: Possible involvement of Her‐2

Cited by 36 publications

References 30 publications

The stage-specific function of gap junctions during tumourigenesis

The stage-specific function of gap junctions during tumourigenesis

Peroxisome proliferator‐activated receptor δ as a molecular target to regulate lung cancer cell growth

Fenofibrate attenuates contact-stimulated cell motility and gap junctional coupling in DU-145 human prostate cancer cell populations

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