Fig. 1 | Signal Transduction and Targeted Therapy

Fig. 1

From: Unmasking metabolic dependencies in pancreatic cancer: aberrant polyamine synthesis as a promising new therapeutic target

Fig. 1

In healthy adults, ornithine is typically produced from arginine through arginase enzymes ARG1 and ARG2 (blue panel). However, the limited availability of arginine in the PDA tumor microenvironment (gray panel) leads to a metabolic shift favoring the unconventional use of glutamine for polyamine synthesis. The KRAS-MEK-KLF6 axis controls the increased expression of genes involved in polyamine synthesis, and inhibiting KRAS or MEK decreases ornithine and putrescine levels. Furthermore, silencing KLF6 reduces the expression of polyamine synthesis genes. In PDA cells, inhibiting OAT with 5-fluoromethylornithine (5-FMO) specifically suppresses the synthesis of ornithine and putrescine derived from glutamine, resulting in reduced tumor growth (orange panel)

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