Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma

Kakuki, Takuya; Kurose, Makoto; Takano, Kenichi; Kondo, Atsushi; Obata, Kazufumi; Nomura, Kazuhiro; Miyata, Ryo; Kaneko, Yakuto; Konno, Takumi; Takahashi, Syunta; Hatakeyama, Tsubasa; Kohno, Takayuki; Himi, Tetsuo; Kojima, Takashi

doi:10.18632/oncotarget.8432

Cited by 36 publications

(42 citation statements)

References 23 publications

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“…Another possibility is that deregulated expression of JAM‐A might be directly associated with cumulative alterations of aberrant signalings such as MAPK, PI3K, and Akt/β‐catenin pathways. This explanation is based on evidence that these signalings are closely associated with various tumor pathologies that are caused by JAM‐A overexpression . It is thus reasonable to assume that dysregulation of JAM‐A leads to the promotion of various malignant behaviors of tumor cells such as cell proliferation, migration, epithelial–mesenchymal transition, and dedifferentiation accompanied by the gain of stem‐cell features …”

Section: Discussionmentioning

confidence: 99%

“…This explanation is based on evidence that these signalings are closely associated with various tumor pathologies that are caused by JAM-A overexpression. (25)(26)(27) It is thus reasonable to assume that dysregulation of JAM-A leads to the promotion of various malignant behaviors of tumor cells such as cell proliferation, migration, epithelial-mesenchymal transition, and dedifferentiation accompanied by the gain of stem-cell features. (17,(25)(26)(27) Results of the present study indicate that JAM-A is not only a possible biomarker for lung adenocarcinoma but also a plausible therapeutic target for this malignancy.…”

Section: Discussionmentioning

confidence: 99%

“…(25)(26)(27) It is thus reasonable to assume that dysregulation of JAM-A leads to the promotion of various malignant behaviors of tumor cells such as cell proliferation, migration, epithelial-mesenchymal transition, and dedifferentiation accompanied by the gain of stem-cell features. (17,(25)(26)(27) Results of the present study indicate that JAM-A is not only a possible biomarker for lung adenocarcinoma but also a plausible therapeutic target for this malignancy. Based on the suppressive effect of an antibody against JAM-A on malignant behaviors of lung adenocarcinoma cells, we believe that specific inactivation of deregulated JAM-A protein would have a notable impact on malignant potential of human tumors with overexpressed JAM-A, suggesting the potential feasibility of JAM-A-inhibitory cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

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Elevated expression of JAM‐A promotes neoplastic properties of lung adenocarcinoma

et al. 2017

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A cell–cell adhesion protein, junctional adhesion molecule‐A (JAM‐A), has been shown to be involved in neoplasia of various organs. However, the fundamental role of JAM‐A in tumorigenesis is still under debate because dysregulated expression of this protein has distinct effects, playing opposite roles in carcinogenesis depending on the target tissues. In the present study, we found elevated levels of JAM‐A expression in lung adenocarcinoma and its preinvasive lesions, including atypical adenomatous hyperplasia and adenocarcinoma in situ by immunohistochemistry. We also showed that suppression of constitutive JAM‐A expression conferred target cells with increased susceptibility to apoptosis in lung adenocarcinoma cells. Consequently, inhibition of JAM‐A activity decreased colony‐forming capability in vitro and tumorigenicity in vivo. The transformed phenotype following suppression of JAM‐A expression was sufficient to reduce motile and invasive capacities. Importantly, knockout of JAM‐A had striking effects on cells. Our observations suggest that increased expression of JAM‐A promotes neoplasia of lung adenocarcinoma. In addition, an anti‐JAM‐A antibody efficiently reduced cell proliferation and provoked apoptosis, indicating the potential feasibility of JAM‐A‐inhibitory cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Elevated expression of JAM‐A promotes neoplastic properties of lung adenocarcinoma

et al. 2017

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“…JAM‐A is deregulated in several human carcinomas, in particular, its low expression is associated with poor prognosis in pancreatic, renal, and gastric cancers . On contrary, recent papers report high expression levels of JAM‐A in nasopharyngeal cancers, head and neck squamous cell carcinoma, non–small‐cell lung cancer, and in multiple myeloma …”

Section: Introductionmentioning

confidence: 99%

Junctional adhesion molecule‐A is down‐regulated in anaplastic thyroid carcinomas and reduces cancer cell aggressiveness by modulating p53 and GSK3 α/β pathways

Orlandella

Mariniello

Iervolino

et al. 2019

Molecular Carcinogenesis

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Junctional adhesion molecule A (JAM‐A) is a transmembrane protein that contributes to different biological process, including the epithelial to mesenchymal transition (EMT). Through an EMT profiler array, we explored the molecular players associated with human thyroid cancer progression and identified JAM‐A as one of the genes mostly deregulated. The quantitative real‐time polymerase chain reaction and immunohistochemistry analyses showed that downregulation of JAM‐A occurred in anaplastic thyroid carcinoma (ATC) compared with normal thyroid (NT) and papillary thyroid carcinoma (PTC) tissues and correlated with extrathyroid infiltration, tumor size, and ATC histotype. In ATC cell lines, JAM‐A restoration suppressed malignant hallmarks of transformation including cell proliferation, motility, and transendothelial migration. Accordingly, knockdown of JAM‐A enhanced thyroid cancer cell proliferation and motility in PTC cells. Through the proteome profiler human phospho‐kinase array, we demonstrated that higher expression of JAM‐A was associated with a significant increased level of phosphorylation of p53 and GSK3 α/β proteins. In conclusion, our findings highlight a novel role of JAM‐A in thyroid cancer progression and suggest that JAM‐A restoration could have potential clinical relevance in thyroid cancer treatment.

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“…P63 is required for key events in keratinocyte adhesion and barrier formation, so it comes as no surprise that claudin‐1 is a direct target of p63 . Overexpression of JAM‐A in head and neck squamous cell carcinoma is regulated through p63 . ΔNp63 has a role in maintaining epithelial integrity in the airway epithelium .…”

Section: Introductionmentioning

confidence: 99%

Regulation of claudin‐4 via p63 in human epithelial cells

Kojima

Kohno

Kubo

et al. 2017

Annals of the New York Academy of Sciences

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P63 is a regulator of cell-cell junction complexes in the epidermis. Claudin-4 is regulated via various factors in normal epithelial cells and diseases. We found that claudin-4 was directly regulated via p63 (TAp63 and ΔNp63) in human keratinocytes and nasal epithelial cells. In the epidermis of atopic dermatitis (AD), which contains ΔNp63-deficient keratinocytes, high expression of claudin-4 was observed. In primary keratinocytes, downregulation of ΔNp63 by treatment with short interfering RNA (siRNA)-p63 induced claudin-4 expression. In nasal epithelial cells in the context of rhinitis or nasal polyps, upregulation of TAp63 and downregulation of claudin-4 were observed. In primary nasal epithelial cells transfected with the human telomerase reverse transcriptase gene, knockdown of p63 by siRNAs induced claudin-4 expression. Taken together, these findings indicate that p63 is a negative regulator of claudin-4 expression. Understanding the regulation of claudin-4 via p63 in human epithelial cells may be important for developing therapies for allergies and drug delivery systems.

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Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma

Abstract: Junctional adhesion molecule-A (JAM-A

Cited by 36 publications

References 23 publications

Elevated expression of JAM‐A promotes neoplastic properties of lung adenocarcinoma

Elevated expression of JAM‐A promotes neoplastic properties of lung adenocarcinoma

Junctional adhesion molecule‐A is down‐regulated in anaplastic thyroid carcinomas and reduces cancer cell aggressiveness by modulating p53 and GSK3 α/β pathways

Regulation of claudin‐4 via p63 in human epithelial cells

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