Abstract:
Mammalian Enabled (Mena) induces unbranched actin polymerization and it acts as an antagonist for actin capping proteins in the cell. As an actin related protein, Mena has an important role on both tumor initiation and metastasis. It has been showed that Mena is upregulated in several types of cancers such as breast, colorectal and cervical cancers. In this study, we aimed to find out the signal transduction pathway of Mena which promotes cancer development. Our primary focus was the dysregulation of the Hippo pathway and one of its effector molecules known as an oncoprotein called YAP. The Hippo signaling pathway is one of the main regulators of tissue growth and it is evolutionary conserved from D. melanogaster to mammals. Understanding the regulation of the Hippo signaling pathway is one of the recent focuses in cancer research field. By using HEK293FT cells, we showed that Mena negatively regulates TEAD promoter binding activity of YAP, which indicates the inhibition of YAP. Both upregulation and downregulation of Mena al-so led to change in total YAP protein levels but this effect seemed to be independent from the Hippo signaling. By using real-time PCR, we found that the level of regulation is on protein levels since RNA levels of YAP homologs did not change by Mena downregula-tion. For in vitro experiments overexpression and knockdown vectors for Mena were used and around 50% reduction in Mena expression was achieved by the knockdown vector. In order to verify this regulation in flies, UAS-GAL4 system is used to cause overexpression of Mena homolog Ena in both wing tissue and follicle cells in the ovary. It is found that Ena overexpression does not have any effect neither on the activitiy of the Hippo signaling nor on the activity of YAP homolog Yki. Further studies may be conducted to find the me-chanism behind this regulation and the affected cellular processes by this regulation.
