Cellular metabolites regulating cancer cell adaptation SAICAR is a metabolite accumulates in cancer cells upon glucose starvation or EGF stimulation. Upon accumulation, SAICAR promotes cancer cell survival and proliferation by inducing tumor PKM2. However, it is not yet clear how cancer cells, but not normal proliferating cells, accumulate SAICAR. We hypothesize that transformation-induced alteration of pentose phosphate pathway is responsible for the accumulation of SAICAR. In this project, we will test this hypothesis while evaluating the importance of SAICAR accumulation for the growth of tumor in vivo. The outcome of this project include a better understanding on metabolic reprogramming contributes to cancer. In addition, the outcome of this project will determine whether SAICAR accumulation can be a potential therapeutic target.
SAICAR is a nucleotide biosynthesis metabolite whose accumulation induces the survival and the proliferation of cultured cancer cells. We will determine the mechanism on how cancer cells but not normally proliferating cells accumulate SAICAR, while testing the relevance to tumor growth in vivo. The outcome will determine whether the SAICAR accumulation can be a potential therapeutic target.
|Yan, Ming; Chakravarthy, Srinivas; Tokuda, Joshua M et al. (2016) Succinyl-5-aminoimidazole-4-carboxamide-1-ribose 5'-Phosphate (SAICAR) Activates Pyruvate Kinase Isoform M2 (PKM2) in Its Dimeric Form. Biochemistry 55:4731-6|
|Keller, Kirstie E; Doctor, Zainab M; Dwyer, Zachary W et al. (2014) SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells. Mol Cell 53:700-9|