Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma.
Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma.
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DOI：
10.18632/oncotarget.8432
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Kojima T
中科院分区：
文献类型：
--
作者：
Kakuki T;Kurose M;Takano K;Kondoh A;Obata K;Nomura K;Miyata R;Kaneko Y;Konno T;Takahashi S;Hatakeyama T;Kohno T;Himi T;Kojima T
连接粘附分子-A（Junctional adhesion molecule-A，JAM-A）属于IgG超家族，是一种与上皮和内皮屏障功能相关的紧密连接分子。JAM-A的过表达还与癌症如乳腺癌、肺癌和胰腺癌的侵袭和转移密切相关。然而，关于JAM-A在头颈部鳞状细胞癌（HNSCC）中过度表达的机制知之甚少。在本研究中，我们发现在HNSCC组织中，包括口咽、喉和下咽部的组织中，JAM-A在蛋白和mRNA水平上高表达，以及β-catenin、p63、Δ Np 63和加塔-3的高蛋白表达。此外，在ELISA中，与健康受试者相比，观察到HNSCC患者血清中可溶性JAM-A的显著增加。siRNA敲低JAM-A可抑制HNSCC细胞系Detroit 562的增殖、侵袭和迁移。JAM-A在Detroit 562中的表达通过包括NF-κB的独特信号转导途径增加。缺氧可降低JAM-A、β-catenin、p63和Δ Np 63在Detroit 562细胞中的表达。通过siRNA敲低p63、Δ Np 63或加塔-3降低底特律562中的JAM-A表达。在检测到CK 7、p63、Δ Np 63和加塔-3的原代培养的HNSCC细胞中，通过敲低p63或Δ Np 63降低JAM-A表达。这些结果表明，JAM-A是HNSCC恶性肿瘤的生物标志物，血浆可溶性JAM-A可能有助于HNSCC的血清诊断。通过p63/加塔-3调控JAM-A的机制对HNSCC的分子靶向治疗具有重要意义。
Junctional adhesion molecule-A (JAM-A), which belongs to the IgG superfamily, is a tight junction molecule associated with epithelial and endothelial barrier function. Overexpression of JAM-A is also closely associated with invasion and metastasis of cancers such as breast cancer, lung cancer and pancreatic cancer. However, little is known about the mechanism in overexpression of JAM-A in head and neck squamous cell carcinoma (HNSCC). In the present study, we found high expression of JAM-A at the protein and mRNA levels in HNSCC tissues, including those of the oropharynx, larynx, and hypopharynx, together with high protein expression of β-catenin, p63, ΔNp63 and GATA-3. Furthermore, in ELISA, a significant increase of soluble JAM-A in the sera of HNSCC patients was observed compared to healthy subjects. Knockdown of JAM-A by siRNA inhibited cell proliferation, invasion and migration in the HNSCC cell line Detroit562 in vitro. JAM-A expression in Detroit562 was increased via a distinct signal transduction pathway including NF-κB. Expression of JAM-A, β-catenin, p63 and ΔNp63 in Detroit562 was decreased under hypoxia. Knockdown of p63, ΔNp63 or GATA-3 by siRNAs reduced JAM-A expression in Detroit562. In primary cultured HNSCC cells in which CK7, p63, ΔNp63 and GATA-3 were detected, JAM-A expression was decreased by knockdown of p63 or ΔNp63. These results indicate that JAM-A is a biomarker of malignancy in HNSCC and that plasma soluble JAM-A may contribute to serum-based diagnosis of HNSCC. The mechanism of dysregulation of JAM-A via p63/GATA-3 is important in possible molecular targeted therapy for HNSCC.
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DOI：
10.1016/j.bbrc.2009.01.100
发表时间：
2009-03-06
影响因子：
3.1
作者：
Gutwein, Paul;Schramme, Anja;Pfeilschifter, Josef
通讯作者：
Pfeilschifter, Josef
DOI：
10.1186/bcr2853
发表时间：
2011-03-23
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
McSherry EA;Brennan K;Hudson L;Hill AD;Hopkins AM
通讯作者：
Hopkins AM
影响因子：
3.3
作者：
Severson, Eric A.;Lee, Winston Y.;Parkos, Charles A.
通讯作者：
Parkos, Charles A.
影响因子：
11.4
作者：
Ebnet, K;Suzuki, A;Vestweber, D
通讯作者：
Vestweber, D
DOI：
10.1111/igc.0b013e31819bc6e9
发表时间：
2009-02-01
影响因子：
4.8
作者：
Koshiba, Hisato;Hosokawa, Kenichi;Honjo, Hideo
通讯作者：
Honjo, Hideo