Molecular association of cancer cell metastasis with signaling pathways has been explicated so as to aid in the development of new prognostic models for better cancer therapies. However, those metastatic signaling pathways are barely explored to take account of the functions of enzymes involved in cellular metabolism. Particularly, the metabolic enzymes in de novo purine biosynthesis have been overlooked for their potential roles in cancer cell metastasis even though they have been successfully validated anti-cancer drug targets. Meanwhile, several lines of recent discoveries on de novo purine biosynthesis suggest that the spatiotemporal assembly of purine biosynthetic enzymes, the purinosome, is under controls of signaling pathways in cancer cells. The results of the inquiry reveal an unanticipated mechanism of action of 3-phosphoinositide-dependent protein kinase 1 (PDK1) signaling pathways in regulation of purine biosynthesis in an Akt-independent manner. Considering the biological action of the Akt-independent PDK1 signaling in anchorage-independent growth of breast cancer cells, we hypothesize that purinosome assembly and disassembly are regulated by Akt-independent PDK1 signaling pathways during breast cancer cell migration and invasion. Collectively, the research coupling two druggable anti-cancer targets will reveal the importance of the heretofore unrecognized molecular interaction between the Akt-independent PDK1 signaling and the purinosome, leading to therapeutic intervention in the management of breast cancer metastasis.

Citation Format: Songon An. Akt-independent PDK1 signaling in regulation of purine biosynthesis. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B13.