Abstract 4770: The regulation of pre-ribosomal RNA synthesis by LKB1

Abstract

Abstract LKB1 is commonly thought of as a tumor suppressor gene, because its hereditary mutation is responsible for a cancer syndrome, and somatic inactivation of LKB1 is found in non-small cell lung cancer, melanoma, and cervical cancers. Unlike other tumor suppressors whose main function is to either suppress cell proliferation or promote cell death, one of the functions of LKB1 is to suppress cell proliferation in order to promote cell survival under energetic stress conditions. We recently discovered that LKB1 promotes pre-ribosomal RNA synthesis under uridine down-regulated condition. The mechanistic basis of this finding is that LKB1 activates TIF-IA-mediated pre-riobosomal RNA synthesis, partly through the control of its cellular localization. Immuno-coprecipitation study revealed that the interaction between TIF-IA and nuclear transportation machinery may be regulated by LKB1. Our finding also has important clinical implication because the suppression of de novo UTP synthesis preferentially promotes apoptosis in LKB1-inactivated cells. This unique, pro-survival function of LKB1 led us to exploit the vulnerability of LKB1-null cells in their defect in sensing intracellular UTP depletion. Such targeted agents represent a novel treatment strategy because they only induce cell killing when LKB1 is absent. Citation Format: Rui Jin, Faken Liu, Xiuju Liu, Henry Huang, Scott C. Wilkinson, Diansheng Zhong, Fadlo R. Khuri, Haian Fu, Adam I. Marcus, Yulong He, Wei Zhou. The regulation of pre-ribosomal RNA synthesis by LKB1. [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 4770.