RICTOR-UGCG Axis: A Molecular Control Panel for Cancer Proliferation. This cartoon visually metaphorizes the intricate molecular mechanisms driving cancer cell proliferation, specifically highlighting a critical fault in metabolic circuitry. The artwork depicts the RICTOR–UGCG signaling axis as a sophisticated control panel, analogous to an electrical switchboard where UGCG is transcriptionally regulated by the transcription factor ZFX. At the heart of this "circuitry" is RICTOR (Rapamycin-Insensitive Companion of mTOR), presented as a master switch, which when activated (switched "ON"), initiates a cascade of signals leading to the deregulation of key epigenetic regulators, DNMT1 and KDM5A. This epigenetic dysregulation, represented by the complex wiring above the RICTOR switch, subsequently enhances the activity of UGCG (UDP-glucose ceramide glucosyltransferase). The heightened UGCG activity results in a significant imbalance in the levels of GD3 and GM1 gangliosides, specifically leading to elevated GD3 levels, which is visually represented on the bioincubator. The elevated GD3 levels activate EGFR (Epidermal Growth Factor Receptor) signaling. EGFR dimerization becomes the driver of uncontrolled cell proliferation, symbolized by the rapidly multiplying cancer cells within the bioincubator glass dome. This interconnected circuitry metaphor illustrates how mTORC2-driven lipid rewiring (via RICTOR and ganglioside metabolism) and epigenetic regulation converge synergistically to promote and sustain tumor progression. Image Credit: Animesh Kar & Mohammad Nafees Ansari (using Procreate).
We know that the mTORC2 complex regulates lipid synthesis in #cancer, but how? This study shows that RICTOR (reg subunit of mTORC2) regulates synthesis of #sphingolipids & #gangliosides by modulating expression of the UGCG enzyme, so promoting #BreastCancer growth @plosbiology.org 🧪 plos.io/42q1Hg4