CD9 negatively regulates CD26 expression and inhibits CD26-mediated enhancement of invasive potential of malignant mesothelioma cells.
CD9 negatively regulates CD26 expression and inhibits CD26-mediated enhancement of invasive potential of malignant mesothelioma cells.
复制标题
DOI：
10.1371/journal.pone.0086671
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Morimoto C
中科院分区：
文献类型：
--
作者：
Okamoto T;Iwata S;Yamazaki H;Hatano R;Komiya E;Dang NH;Ohnuma K;Morimoto C
CD 26/二肽基肽酶IV是一种细胞表面糖蛋白，除了其外肽酶位点外，还包括多个功能结构域。越来越多的证据表明，CD 26的表达升高与选定的恶性肿瘤的疾病侵袭性和侵袭潜力相关。为了进一步探讨这种临床行为的分子机制，我们目前的工作集中在CD 26和CD 9之间的相互作用，这是最近被确定为恶性间皮瘤中癌症干细胞的新标志物。我们发现CD 26和CD 9在恶性间皮瘤细胞系ACC-MESO 1和MSTO-211 H中相互共调节和共沉淀。SiRNA研究显示，CD 26的缺失导致CD 9表达增加，而CD 9的缺失导致CD 26表达增加。与这些发现一致的是，将CD 26基因转移到CD 26阴性MSTO-211 H细胞中降低了CD 9表达。细胞侵袭实验表明，CD 26过表达或CD 9基因缺失可导致侵袭能力增强，而CD 26基因缺失则导致侵袭能力降低。此外，我们的工作表明，这种增强的侵袭性可能部分由α5β1整联蛋白介导，因为共沉淀研究表明CD 26和α5β1整联蛋白之间存在关联。最后，CD 9的基因缺失导致FAK和Cas-L的蛋白水平和酪氨酸磷酸化升高，FAK和Cas-L是β1整联蛋白的下游，而CD 26的缺失导致这些分子的水平降低。总的来说，我们的研究结果表明，CD 26通过与α5β1整合素的相互作用增强肿瘤细胞的侵袭，而CD 9通过降低CD 26-α5β1整合素复合物的水平，通过CD 9和CD 26表达之间的负相关性，负调节肿瘤细胞的侵袭。我们的研究结果还表明，CD 26和CD 9作为潜在的生物标志物，以及有前途的分子靶点的新的治疗方法，在恶性间皮瘤和其他恶性肿瘤。
CD26/dipeptidyl peptidase IV is a cell surface glycoprotein which consists of multiple functional domains beside its ectopeptidase site. A growing body of evidence indicates that elevated expression of CD26 correlates with disease aggressiveness and invasive potential of selected malignancies. To further explore the molecular mechanisms involved in this clinical behavior, our current work focused on the interaction between CD26 and CD9, which were recently identified as novel markers for cancer stem cells in malignant mesothelioma. We found that CD26 and CD9 co-modulated and co-precipitated with each other in the malignant mesothelioma cell lines ACC-MESO1 and MSTO-211H. SiRNA study revealed that depletion of CD26 led to increased CD9 expression, while depletion of CD9 resulted in increased CD26 expression. Consistent with these findings was the fact that gene transfer of CD26 into CD26-negative MSTO-211H cells reduced CD9 expression. Cell invasion assay showed that overexpression of CD26 or gene depletion of CD9 led to enhanced invasiveness, while CD26 gene depletion resulted in reduced invasive potential. Furthermore, our work suggested that this enhanced invasiveness may be partly mediated by α5β1 integrin, since co-precipitation studies demonstrated an association between CD26 and α5β1 integrin. Finally, gene depletion of CD9 resulted in elevated protein levels and tyrosine phosphorylation of FAK and Cas-L, which are downstream of β1 integrin, while depletion of CD26 led to a reduction in the levels of these molecules. Collectively, our findings suggest that CD26 potentiates tumor cell invasion through its interaction with α5β1 integrin, and CD9 negatively regulates tumor cell invasion by reducing the level of CD26-α5β1 integrin complex through an inverse correlation between CD9 and CD26 expression. Our results also suggest that CD26 and CD9 serve as potential biomarkers as well as promising molecular targets for novel therapeutic approaches in malignant mesothelioma and other malignancies.
登录
查看更多内容
影响因子：
4.2
作者：
Amatya VJ;Takeshima Y;Aoe K;Fujimoto N;Okamoto T;Yamada T;Kishimoto T;Morimoto C;Inai K
通讯作者：
Inai K
影响因子：
11.2
作者：
Furuya, M;Kato, F;Ishikura, H
通讯作者：
Ishikura, H
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
23.9
作者：
Pang, Roberta;Law, Wai Lun;Wong, Benjamin C. Y.
通讯作者：
Wong, Benjamin C. Y.
影响因子：
8
作者：
Huang, C-L;Ueno, M.;Miyake, M.
通讯作者：
Miyake, M.