Human squamous-cell-carcinoma cell line (DJM-1) cells synthesize P-cadherin moleculesvia an elevation of extracellular calcium: Calcium regulates P-cadherin-gene expression at the translational levelvia protein tyrosine phosphorylation

Wakita, Hisashi; Furukawa, Fukumi; Baba, Satoshi; Takigawa, Masaharu

doi:10.1002/(sici)1097-0215(19971104)73:3<432::aid-ijc19>3.0.co;2-e

Cited by 10 publications

(4 citation statements)

References 18 publications

(20 reference statements)

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“…These results were not surprising. In previous works, measurable phosphorylation of Dsg 3 was demonstrated using the DJM-1 cutaneous squamous cell carcinoma cell line, which features high levels of phosphorylation of adhesion molecules and, therefore, is customarily used to study phosphorylation of keratinocyte adhesion molecules (61)(62)(63)(64). In contrast to DJM-1 cells, PV IgG produces only minor changes in the level of phosphorylation of Dsg 3 in normal human KCs (11).…”

Section: Discussionmentioning

confidence: 99%

Differential Coupling of M1 Muscarinic and α7 Nicotinic Receptors to Inhibition of Pemphigus Acantholysis

Chernyavsky

Arredondo

Piser

et al. 2008

Journal of Biological Chemistry

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The mechanisms mediating and regulating assembly and disassembly of intercellular junctions is a subject of intensive research. The IgG autoantibodies produced in patients with the immunoblistering skin disease pemphigus vulgaris (PV) can induce keratinocyte (KC) dyshesion (acantholysis) via mechanisms that involve signaling kinases targeting intercellular adhesion molecules, thus providing a useful model to study the physiologic regulation of KC cohesion. Previous studies showed that activation of Src and protein kinase C are the earliest events in the PV IgG-induced intracellular phosphorylation cascades and that cholinergic agonists are effective for treating patients with pemphigus. In this study, we sought to elucidate the molecular mechanisms allowing cholinergic agonists to inhibit PV IgG-induced acantholysis and phosphorylation of KC adhesion molecules. The extent of acantholysis in KC monolayers correlated closely with the degree of PV IgG-induced phosphorylation of p120-and ␤-catenins, with classic isoforms of protein kinase C mediating serine phosphorylation of ␤-catenin and Src-tyrosine phosphorylation of p120-catenin. The M 1 muscarinic agonist pilocarpine blocked phosphorylation of both catenins, which could be abolised by the M 1 antagonist MT7. The ␣7 nicotinic agonist AR-R17779 inhibited phosphorylation of P120-cateinin. The ␣7 antagonist methyllycaconitine abolished the effect of AR-R17779. Okadaic acid abrogated protective effects of agonists on phosphorylation of ␤-catenin, and pervanadate, on that of p120-catenin. Stimulation of KCs with pilocarpine significantly (p < 0.05) elevated both serine/threonine and tyrosine phosphatase activities in KCs. AR-R17779 both stimulated tyrosine phosphatase and decreased PV IgGinduced Src activity. Methyllycaconitine released Src activity in intact KCs and caused acantholysis. Thus, downstream signaling from M 1 abolished PV IgG-dependent catenin phosphorylation due to activation of both serine/threonine and tyrosine phosphatases, whereas ␣7 action involved both activation of tyrosine phosphatase and inhibition of Src. These findings identified novel paradigm of regulation of signaling kinases associated with cholinergic receptors and provided mechanistic explanation of therapeutic activity of cholinomimetics in PV patients.

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Section: Discussionmentioning

confidence: 99%

Differential Coupling of M1 Muscarinic and α7 Nicotinic Receptors to Inhibition of Pemphigus Acantholysis

Chernyavsky

Arredondo

Piser

et al. 2008

Journal of Biological Chemistry

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“…Recent research convincingly demonstrated that the molecular mechanism of cholinergic acantholysis involves an antagonist‐induced phosphorylation of KC adhesion molecules. The effects of muscarinic and nicotinic antagonists on the phosphorylation status of E‐cadherin and β‐ and γ‐catenins were measured in the DJM‐1 cell line of immortal KCs that feature high levels of phosphorylation of adhesion molecules (52–56). Treatment of DJM‐1 cells with atropine increased the phosphorylation level of E‐cadherin by approximately 120%, that of Dsg 3 by 33%, and that of β‐ and γ‐catenin by 50%, whereas mecamylamine produced only minor changes in the phosphorylation status of KC adhesion molecules (24,45).…”

Section: Cholinergic Control Of Keratinocyte Cell–cell Adhesion (Tablmentioning

confidence: 99%

Cholinergic control of epidermal cohesion

Grando

2006

Experimental Dermatology

124

111

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The non-neuronal cholinergic system of human epidermis includes the keratinocyte (KC) acetylcholine (ACh) axis composed of the enzymes mediating ACh synthesis and degradation, and two classes of ACh receptors, the nicotinic and muscarinic ACh receptors, mediating biological effects of the cutaneous cytotransmitter ACh. Regulation of KC cell-cell and cell-matrix adhesion is one of the important biological functions of cutaneous ACh. The downstream targets of ACh effects mediated by distinct ACh receptor subtypes include both the intercellular adhesion molecules, such as classical and desmosomal cadherins, and integrins mediating KC adhesion to a substrate. The signaling pathways include activation or inhibition of kinase cascades resulting in either up-or down-regulation of the expression of cell adhesion molecules or changes in their phosphorylation status, or both. The components of the KC ACh axis are involved in cutaneous blistering in patients with autoimmune pemphigus, junctional and dystrophic forms of epidermolysis bullosa, thermal burns, and mustard-induced vesication. Recent progress with the development of antiacantholytic therapies of patients with pemphigus using cholinomimetics indicates that cholinergic drugs may be a promising approach for other cutaneous blistering disorders.

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“…E-cad is expressed on all epithelial layers, while P-cad is predominantly expressed in the basal layer of stratified squamous epithelia, the proliferative compartment [54-59]. E- and P-cad expression is altered in premalignant and malignant skin tumors, as demonstrated by reduced E-cad and aberrant P-cad expression in human squamous cell carcinomas [59], indicating the importance of coordinated cadherin expression for maintaining normal epidermal structure [60]. Malignant keratinocytes probably acquire different mechanisms for regulating the expression of these two cadherins [61].…”

Section: Discussionmentioning

confidence: 99%

“…SCC cells probably acquire the ability to express P-cad and this molecule plays a role in tumour progression [61]. Elevated [Ca ++ ] determined increased cell-surface P-cad expression in SCC cell lines by up-regulation of de novo P-cad synthesis, while in normal keratinocytes calcium-induced cell-surface P-cad expression is a result of the translocation of pre-formed P-cad from the cytosol without up-regulation of P-cad synthesis [60]. These results suggest the existence of a unique mechanism for regulating the P-cad expression gene in tumour cells.…”

Section: Discussionmentioning

confidence: 99%

P-cadherin expression and survival rate in oral squamous cell carcinoma:an immunohistochemical study

et al. 2005

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Background: P-cadherin (P-cad) is a transmembrane molecule involved in the cell-cell adhesion and similar to E-cadherin (E-cad), but less investigated in oncology, especially in in vivo studies. Aims of the present study were to assess the prevalence of P-cad expression in oral squamous cell carcinoma (OSCC) and to verify whether P-cad can be considered a marker of prognosis in patients with OSCC.

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Human squamous-cell-carcinoma cell line (DJM-1) cells synthesize P-cadherin moleculesvia an elevation of extracellular calcium: Calcium regulates P-cadherin-gene expression at the translational levelvia protein tyrosine phosphorylation

Cited by 10 publications

References 18 publications

Differential Coupling of M1 Muscarinic and α7 Nicotinic Receptors to Inhibition of Pemphigus Acantholysis

Differential Coupling of M1 Muscarinic and α7 Nicotinic Receptors to Inhibition of Pemphigus Acantholysis

Cholinergic control of epidermal cohesion

P-cadherin expression and survival rate in oral squamous cell carcinoma:an immunohistochemical study

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