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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sun, Fenyong Wang, Jiayi Pan, Qiuhui Yu, Yongchun Ma, Lifang Lin, Jiafei |
| Description | Author Affiliation: Ma L ( From the Department of Clinical Laboratory Medicine, 301 Middle Yanchang Rd., Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China.) |
| Abstract | Cluster of differentiation 166 (CD166 or Alcam) is a cell surface molecule that can be greatly induced in liver cancer cells after serum deprivation, suggesting its role in influencing cell survival. However, whether and how CD166 acts as an anti-apoptotic regulator needs to be further investigated. Here, we report that gene silencing of CD166 promoted apoptosis via down-regulation of Bcl-2 in liver cancer cells. PI3K/AKT signaling was found to up-regulate CD166 expression independently of transcription. We also revealed that CD166 promoted both AKT expression and activity, thus providing a novel positive regulatory feedback between PI3K/AKT signaling and CD166. Moreover, Yes-associated protein (YAP) was identified as a CD166 downstream effecter, which can partly rescue CD166 knockdown-induced apoptosis and reduced in vivo cancer cell growth. Mechanically, CD166 modulated YAP expression and activity through at least two different ways, transcriptional regulation of YAP through cAMP-response element-binding protein and post-transcriptional control of YAP stability through inhibition to AMOT130. We also showed that CD9 enhanced CD166-mediated regulation of YAP via a mechanism involving facilitating CD166-CD166 homophilic interaction. Tissue microarray analysis revealed that CD166 and YAP were up-regulated and closely correlated in liver cancer samples, demonstrating the importance of their relationship. Taken together, this work summarizes a novel link between CD166 and YAP, explores the interplay among related important signaling pathways, and may lead to more effective therapeutic strategies for liver cancer. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 10 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-03-07 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adaptor Proteins, Signal Transducing Metabolism Antigens, CD Biosynthesis Apoptosis Cell Adhesion Molecules, Neuronal Fetal Proteins Liver Neoplasms Phosphatidylinositol 3-Kinases Phosphoproteins Proto-Oncogene Proteins C-akt Genetics Hep G2 Cells Pathology Signal Transduction Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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