Aberrant expression of junctional adhesion molecule-A contributes to the malignancy of cervical adenocarcinoma by interaction with poliovirus receptor/CD155.
Aberrant expression of junctional adhesion molecule-A contributes to the malignancy of cervical adenocarcinoma by interaction with poliovirus receptor/CD155.
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DOI：
10.1111/cas.14734
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发表时间：
2021-03
期刊：
影响因子：
5.7
通讯作者：
Osanai M
中科院分区：
文献类型：
--
作者：
Murakami T;Takasawa A;Takasawa K;Akimoto T;Aoyama T;Magara K;Saito Y;Ota M;Kyuno D;Yamamoto S;Hasegawa T;Saito T;Osanai M
最近的研究表明，紧密连接蛋白(TJP)的异常表达与多种癌症的恶性潜能有关。在本研究中，我们研究了跨膜型TJP之一的交界性黏附分子-A(JAM-A)在子宫颈腺癌中的表达及其在恶变中的意义。免疫组织化学结果显示，JAM-A在包括原位腺癌(AIS)在内的肿瘤组织中有异常表达。JAM-A基因敲除可显著抑制细胞增殖、克隆形成和迁移能力。我们还发现，针对JAM-A胞外区的抗体降低了细胞的增殖能力，而JAM-A的缺失增加了宫颈癌细胞对药物的敏感性。综合蛋白质组学分析，我们发现脊灰病毒受体(PVR/CD155)受JAM-A调控并与JAM-A形成物理相互作用。在手术标本中，PVR/CD155的表达与宫颈腺癌的某些临床病理特征和预后密切相关。有趣的是，大多数PVR/CD155阳性患者表达高水平的JAM-A，且PVR/CD155阳性/JAM-A高表达患者的无复发生存期(P=0.00964)和总生存期(P=0.0204)显著短于其他患者。我们的观察表明，JAM-A的异常表达通过调节PVR/CD155促进了子宫腺癌的恶性，因此JAM-A是治疗这一恶性肿瘤的潜在靶点。连接黏附分子-A(JAM-A)是一种跨膜紧密连接蛋白，其异常表达与子宫腺癌的恶性潜能有关。我们还发现，JAM-A的缺失降低了宫颈癌细胞的耐药性，抗JAM-A抗体抑制了细胞的增殖，表明JAM-A是该病潜在的治疗靶点。此外，我们还发现JAM-A和脊髓灰质炎病毒受体(PVR/CD155)之间的一种新的相互作用与宫颈腺癌的预后不良有关。
Recent studies have shown that aberrant expression of tight junction proteins (TJP) contributes to malignant potential of various cancers. In the present study, we investigated the expression of junctional adhesion molecule‐A (JAM‐A), one of the transmembrane TJP, in uterine cervical adenocarcinoma and the significance of its expression for malignancy. Immunohistochemistry on human surgical specimens showed that JAM‐A was aberrantly expressed in neoplastic regions including adenocarcinoma in situ (AIS). Knockout of JAM‐A significantly suppressed cell proliferation and colony‐forming and migration abilities. We also showed that an antibody specific to an extracellular region of JAM‐A reduced cell proliferation ability and that loss of JAM‐A increased drug sensitivity of cervical adenocarcinoma cells. Based on a comprehensive proteome analysis, we found that poliovirus receptor (PVR/CD155) was regulated by JAM‐A and formed a physical interaction with JAM‐A. In human surgical specimens, PVR/CD155 expression was significantly correlated with some clinicopathological features and prognosis of cervical adenocarcinoma. Interestingly, most of the PVR/CD155‐positive cases expressed a high level of JAM‐A, and patients with the expression pattern of PVR/CD155 positive/JAM‐A high had significantly shorter periods of relapse‐free survival (P = .00964) and overall survival (P = .0204) than those for the other patients. Our observations suggest that aberrant expression of JAM‐A promotes malignancy of uterine cervical adenocarcinoma by regulation of PVR/CD155, and JAM‐A is therefore a potential therapeutic target for this malignancy. Aberrant expression of junctional adhesion molecule‐A (JAM‐A), one of the transmembrane tight junction proteins, contributes to the malignant potential of uterine cervical adenocarcinoma. We also show that loss of JAM‐A attenuated drug resistance of cervical adenocarcinoma cells and that an anti‐JAM‐A antibody inhibited cell proliferation, indicating that JAM‐A is a potential therapeutic target of the malignancy. Moreover, we show that a novel interaction between JAM‐A and poliovirus receptor (PVR/CD155) is associated with worse prognosis of cervical adenocarcinoma.
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DOI：
10.1016/j.neo.2018.08.010
发表时间：
2018-10
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Akimoto T;Takasawa A;Takasawa K;Aoyama T;Murata M;Osanai M;Saito T;Sawada N
通讯作者：
Sawada N
影响因子：
5.7
作者：
Magara K;Takasawa A;Osanai M;Ota M;Tagami Y;Ono Y;Takasawa K;Murata M;Hirohashi Y;Miyajima M;Yamada G;Hasegawa T;Sawada N
通讯作者：
Sawada N
对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
影响因子：
5.7
作者：
Sato, T;Irie, K;Takai, Y
通讯作者：
Takai, Y
DOI：
10.1073/pnas.97.1.79
发表时间：
2000-01-04
影响因子：
11.1
作者：
He, YN;Bowman, VD;Rossmann, MG
通讯作者：
Rossmann, MG