Abstract 2887: Autonomous nucleolar mechanism of colon cancer cell survival through induction of perinuclear ribosomal protein translation

Abstract

Abstract Hypertrophic and irregularly shaped nucleoli are characteristic of gastroitinal cancers with poor prognosis. The role of nucleolar hypertrophy in cancer cell survival has not been studied well. By suppressing several cellular pathways we observed a common cellular response mechanism that involves acceleration of perinuclear ribosomal protein synthesis and multifocal nucleoli hypertrophy. Paradoxically, the induction of perinuclear ribosomal protein biosynthesis was observed by inhibition of protein translation, suppression of protein degradation and mitochondrial activity. Acceleration of perinuclear protein translation in combination of nuclear hypertrophy was detected not only in actively dividing cells but also in quiescent, cell cycle arrested cells, and when cytotoxic effects were manifested. Intensification of perinuclear ribosomal protein translation and nucleolar hypertrophy by Rotenone-mediated damage of mitochondria supported a century long Otto Warburg observation that most cancer cells predominantly produce energy by high rate of glycolysis. Cell fractionation permitted detection of a perinuclear wall that provides a structural basis for the perinuclear protein translation. We found that that rapid- and slow-growing colon cancer cells significantly differ by abundance of ribosomes in the perinuclear region. Therefore, the perinuclear set of protein translation is an important mechanism of cancer cell survival that rescues ribosome biogenesis and leads to the drug resistance through nuclear transformation. Citation Format: Tattym E. Shaiken, Antone R. Opekun. Autonomous nucleolar mechanism of colon cancer cell survival through induction of perinuclear ribosomal protein translation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2887.