Cluster of Differentiation 166 (CD166) regulated by Phosphatidylinositide 3-Kinases (PI3K)/AKT signaling to exert its anti-apoptotic role via Yes associated protein (YAP) in liver cancer [Signal Transduction]

January 30th, 2014 by Ma, L., Wang, J., Lin, J., Pan, Q., Yu, Y., Sun, F.

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 reported that gene silencing of CD166 promoted apoptosis via down-regulation of Bcl-2 in liver cancer cells. PI3K/AKT signaling was found up-regulated CD166 expression independent 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, 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 CREB 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 (TMA) 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 summarized a novel link between CD166 and YAP, explore the interplay among related important signaling pathways may lead to more effective therapeutic strategies for liver cancer.
  • Posted in Journal of Biological Chemistry, Publications
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