Abstract 3422: N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity

Abstract 80%-90% of eukaryotic proteins are N-α-terminally acetylated. They are mediated by specific N-α-acetyltransferases. However, the biological importance of these N-α-acetyltransferases remains largely unknown. Recently, these N-α-acetyltransferases have been recognized as important characters in many biological processes, including embryonic development, neuron disease and cancer. N-α-acetyltransferase A (Nat A) was first characterized in yeast, it composed of Naa10p, also known as hARD1 (human Arrest defective 1), and Naa15p, also known as NATH (N-acetyl transferase human), are responsible for the N-α-acetylation of majority proteins in mammalian cells. Naa10p is known to be involved in cell cycle control and apoptosis. However, the role of Naa10p in human cancers is elusive. In this study, we found that elevated Naa10p levels are associated with less metastasis to lymph nodes and better prognosis of cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells. Our study not only highlights the potential of Naa10p as a therapeutic target for tumor metastasis, but also identifies Naa10p as a regulatory component of the migration complex PIX-GIT-Paxillin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3422. doi:1538-7445.AM2012-3422