Localization of aPKC lambda/iota and its interacting protein, Lgl2, is significantly associated with lung adenocarcinoma progression.
Localization of aPKC lambda/iota and its interacting protein, Lgl2, is significantly associated with lung adenocarcinoma progression.
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发表时间：
2013-12
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通讯作者：
Naoko Imamura;Yosuke Horikoshi;T. Matsuzaki;Kentaro Toriumi;K. Kitatani;G. Ogura;R. Masuda;N. Nakamura;S. Takekoshi;M. Iwazaki
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作者：
Naoko Imamura;Yosuke Horikoshi;T. Matsuzaki;Kentaro Toriumi;K. Kitatani;G. Ogura;R. Masuda;N. Nakamura;S. Takekoshi;M. Iwazaki
非典型蛋白激酶C λ/i（aPKC λ/i）在几种人类癌症中表达;然而，aPKC λ/i定位与人类肺腺癌（LAC）中癌症进展之间的相关性仍有待澄清。我们发现在LAC中具有高水平aPKC λ/ι表达的患者比具有低水平aPKC λ/ι表达的患者具有显著更短的总生存期。此外，aPKC λ/1在顶膜或细胞-细胞接触处的定位与淋巴侵袭和转移两者相关。在肿瘤细胞浸润部位高表达aPKC λ/ι的拉克中，细胞间粘附分子E-cadherin表达减少。提示aPKC λ/i和E-cadherin的表达水平反映了LAC的进展。在双重免疫组织化学分析中，aPKC λ/1和Lgl 2（一种与aPKC λ/1相互作用的蛋白质）共定位于拉克内。此外，我们通过免疫共沉淀分析发现Lgl 2结合肿瘤组织中的aPKC λ/1-Par 6复合物。Lgl 2的顶膜定位与淋巴管浸润和淋巴结转移相关。因此，这些结果表明，aPKC λ/1表达在LAC进展时改变。这也是第一个证据表明aPKC λ/1在LAC中过表达，并证明aPKC λ/1定位在顶端膜或细胞-细胞接触处与肿瘤的淋巴侵袭和转移相关。
Atypical protein kinase C lambda/iota (aPKC λ/ι) is expressed in several human cancers; however, the correlation between aPKC λ/ι localization and cancer progression in human lung adenocarcinoma (LAC) remains to be clarified. We found that patients with a high level of aPKC λ/ι expression in LAC had significantly shorter overall survival than those with a low level of aPKC λ/ι expression. In addition, localization of aPKC λ/ι in the apical membrane or at the cell-cell contact was associated with both lymphatic invasion and metastasis. The intercellular adhesion molecule, E-cadherin, was decreased in LACs with highly expressed aPKC λ/ι at the invasion site of tumor cells. This result suggested that the expression levels of aPKC λ/ι and E-cadherin reflect the progression of LAC. On double-immunohistochemical analysis, aPKC λ/ι and Lgl2, a protein that interacts with aPKC λ/ι, were co-localized within LACs. Furthermore, we found that Lgl2 bound the aPKC λ/ι-Par6 complex in tumor tissue by immune-cosedimentation analysis. Apical membrane localization of Lgl2 was correlated with lymphatic invasion and lymph node metastasis. These results thus indicate that aPKC λ/ι expression is altered upon the progression of LAC. This is also the first evidence to show aPKC λ/ι overexpression in LAC and demonstrates that aPKC λ/ι localization at the apical membrane or cell-cell contact is associated with lymphatic invasion and metastasis of the tumor.