Abstract A25: Effect of Rab25 on Akt1 phosphorylation

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease and despite therapeutic improvements and reconstructive modalities, the overall survival rate remains relatively poor. Although, tobacco and alcohol consumption are recognized as critical risk factors, genetic and epigenetics factors and viral infections also contribute to the progression of HNSCC. Several studies have assessed the status of known oncogenes and tumor suppressor genes to identify novel genomic events in HNSCC. Rab25 belongs to the Rab family of small GTPases. Rab25 has been described in conflicting previous studies as a promoter or suppressor of cancer. More recently, Zhang et al. reported that overexpression of Rab25 contributes to metastasis through activation of the Akt/GSK-3β/Snail pathway signaling in bladder cancer, which act as molecular switches that belong to the Ras protein superfamily and regulate vesicle trafficking in eucaryotic cells. The phosphotidylinositol 3-Kinase (PI3K) signaling pathway plays a critical role in cellular growth, proliferation and survival. Signaling through this pathway is commonly upregulated during tumorigenesis. Akt/PKB is a Ser/Thr kinase and the central member of the PI3K/Akt signaling pathway. It is activated by phosphorylation and subsequently phosphorylates diverse growth –controlling effectors and regulates the synthesis, stability and subcellular localization of cell cycle regulators. In this study, we investigated the phosphorylation of Akt1 and whether it occurs under the effect of Rab25 expression in HNSCC. For this purpose we analyzed the Rab25 protein by Western Blot in 57 HNSCC tumors and corresponding non-cancerous tissue samples. To detect the effect of the Rab25 protein on Akt1 activation we also analyzed the amount of total Akt1 and phosphorylated Akt1 in the same tissue samples. Our results indicate that Rab25 is down-regulated in 56.2% of the HNSCC tumor samples compared to their normal counterparts. On the other hand, the change in Akt1 phosphorylation was in the same direction with Rab25 protein expression (p: 0.04) Citation Format: Nur Buyru, Didem Seven, Soydan Dogan, Hikmet Koseoglu, Emin Karaman. Effect of Rab25 on Akt1 phosphorylation. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A25.