Inhibition of E-Cadherin Dependent Cell-Cell Contact Promotes MUC5AC Mucin Production through the Activation of Epidermal Growth Factor Receptors

Iwashita, Jun; Ose, Kyohei; Ito, Hiroki; Murata, Jun; Abé, Tatsuya

doi:10.1271/bbb.100830

Cited by 10 publications

(13 citation statements)

References 21 publications

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“…c). These findings are consistent with previous results using cultured cells, which demonstrated a downregulatory role of COL4 and E‐cadherin on MUC5AC‐negative expression …”

Section: Resultssupporting

confidence: 93%

“…These findings suggest that the gastric cancer acquired an EMT phenotype whereas the EMPD did not. The results of MUC5AC expression that were confirmed in the EMT phenotype cells but not in the non‐EMT tumour cells are compatible with previous reports using cultured cells in vitro …”

Section: Discussionsupporting

confidence: 92%

“…[3][4][5] Recently, type IV collagen (COL4), a major component of the basal lamina, and E-cadherin were shown to downregulate MUC5AC expression in cultured cells. [6][7][8] However, it has not been known whether COL4/E-cadherin affects MUC5AC expression in tumours in vivo. To address this question, it would be desirable to investigate several types of tumours.…”

Section: What Does This Study Add?mentioning

confidence: 99%

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Concomitant neoplasms in the skin and stomach unveil the role of type IV collagen and E-cadherin in mucin core protein 5AC expression in vivo

et al. 2015

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Mucin core protein (MUC) 5AC is a gel-forming glycoprotein that is expressed in different types of tumour cells. MUC5AC expression in cultured cells is regulated through the extracellular matrix and through remodelling by other membranous proteins such as type IV collagen (COL4) and E-cadherin. However, it has not been elucidated whether COL4 and E-cadherin affect MUC5AC expression in tumours in vivo. Here, by analysing a single individual with concomitant neoplasms in the skin [extramammary Paget disease (EMPD)] and the stomach (gastric cancer), we show that MUC5AC expression is reduced in COL4 and membranous E-cadherin-expressing EMPD specimens whereas MUC5AC is not abolished in gastric cancer with COL4 negativity and E-cadherin cytoplasmic localization. As the EMPD and gastric cancer specimens were derived from a single patient, each specimen had the same genetic background. These in vivo results support previous in vitro studies which showed that COL4 and E-cadherin downregulated MUC5AC expression. Our study suggests that concomitant neoplasms in different organs of the same individual can serve as a strong tool for uncovering functional diversity in tumour markers in distinct cancer cells.

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“…c). These findings are consistent with previous results using cultured cells, which demonstrated a downregulatory role of COL4 and E‐cadherin on MUC5AC‐negative expression …”

Section: Resultssupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: What Does This Study Add?mentioning

confidence: 99%

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Concomitant neoplasms in the skin and stomach unveil the role of type IV collagen and E-cadherin in mucin core protein 5AC expression in vivo

et al. 2015

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“…Cadherin junctions between beta-cells promote improved survival and function [20], and it is possible that also cadherin junctions between NCSC and beta-TC6 cells exert similar effects. The cadherin-induced signaling pathways that mediate resistance to cell death are probably highly complex and context dependent, but studies have reported increased calcium inflow [27], decreased beta-catenin nuclear translocation [28] and decreased ERK phosphorylation [29] as possible down-stream signaling events.…”

Section: Discussionmentioning

confidence: 99%

Co-Culture of Neural Crest Stem Cells (NCSC) and Insulin Producing Beta-TC6 Cells Results in Cadherin Junctions and Protection against Cytokine-Induced Beta-Cell Death

et al. 2013

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PurposeTransplantation of pancreatic islets to Type 1 diabetes patients is hampered by inflammatory reactions at the transplantation site leading to dysfunction and death of insulin producing beta-cells. Recently we have shown that co-transplantation of neural crest stem cells (NCSCs) together with the islet cells improves transplantation outcome. The aim of the present investigation was to describe in vitro interactions between NCSCs and insulin producing beta-TC6 cells that may mediate protection against cytokine-induced beta-cell death.ProceduresBeta-TC6 and NCSC cells were cultured either alone or together, and either with or without cell culture inserts. The cultures were then exposed to the pro-inflammatory cytokines IL-1β and IFN-γ for 48 hours followed by analysis of cell death rates (flow cytometry), nitrite production (Griess reagent), protein localization (immunofluorescence) and protein phosphorylation (flow cytometry).ResultsWe observed that beta-TC6 cells co-cultured with NCSCs were protected against cytokine-induced cell death, but not when separated by cell culture inserts. This occurred in parallel with (i) augmented production of nitrite from beta-TC6 cells, indicating that increased cell survival allows a sustained production of nitric oxide; (ii) NCSC-derived laminin production; (iii) decreased phospho-FAK staining in beta-TC6 cell focal adhesions, and (iv) decreased beta-TC6 cell phosphorylation of ERK(T202/Y204), FAK(Y397) and FAK(Y576). Furthermore, co-culture also resulted in cadherin and beta-catenin accumulations at the NCSC/beta-TC6 cell junctions. Finally, the gap junction inhibitor carbenoxolone did not affect cytokine-induced beta-cell death during co-culture with NCSCs.ConclusionIn summary, direct contacts, but not soluble factors, promote improved beta-TC6 viability when co-cultured with NCSCs. We hypothesize that cadherin junctions between NCSC and beta-TC6 cells promote powerful signals that maintain beta-cell survival even though ERK and FAK signaling are suppressed. It may be that future strategies to improve islet transplantation outcome may benefit from attempts to increase beta-cell cadherin junctions to neighboring cells.

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“…[8][9][10] MUC5AC production is regulated in various ways, such as by inflammatory cytokines (interleukin-1β, tumor necrosis factor-α), cell-cell adhesion molecules, and EGF receptors. 11,12) However, little is known about the regulation of MUC5B production. In a previous study, we reported that several extracellular matrix (ECM) components are involved in the regulation of MUC5AC production.…”

mentioning

confidence: 99%

MUC5B mucin production is upregulated by fibronectin and laminin in human lung epithelial cells via the integrin and ERK dependent pathway

Ito

Iwashita

Kudoh

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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MUC5B mucin is a principal component of airway mucus and plays a key role in biodefense. We investigated the regulation of MUC5B production using the signals from extracellular matrix (ECM) components in NCI-H292 human lung epithelial cells. We found that MUC5B production in NCI-H292 cells cultured on fibronectin or laminin increased by 4–5-fold, with the increase occurring in a dose- and time-dependent manner. In contrast, MUC5B production was unchanged on type-IV collagen. Inhibition of integrin β1 induced upregulation of MUC5B and MUC5AC; however, inhibition of p38 MAPK did not show any remarkable change in overproduced MUC5B. Inhibition of extracellular signal-regulated kinase (ERK) pathway or the transcription factor NF-κB induced the recovery of overproduced MUC5B on fibronectin and laminin. These results suggest that MUC5B production can be regulated by ECM components and that MUC5B is upregulated by fibronectin and laminin via the integrin, ERK, and NF-κB dependent pathway.

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Inhibition of E-Cadherin Dependent Cell-Cell Contact Promotes MUC5AC Mucin Production through the Activation of Epidermal Growth Factor Receptors

Cited by 10 publications

References 21 publications

Concomitant neoplasms in the skin and stomach unveil the role of type IV collagen and E-cadherin in mucin core protein 5AC expression in vivo

Concomitant neoplasms in the skin and stomach unveil the role of type IV collagen and E-cadherin in mucin core protein 5AC expression in vivo

Co-Culture of Neural Crest Stem Cells (NCSC) and Insulin Producing Beta-TC6 Cells Results in Cadherin Junctions and Protection against Cytokine-Induced Beta-Cell Death

MUC5B mucin production is upregulated by fibronectin and laminin in human lung epithelial cells via the integrin and ERK dependent pathway

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