Inhibition of Tumor Lipogenesis and Growth by Peptide-Based Targeting of SREBP Activation.

ABSTRACT: Tumor cells have substantially increased lipid biogenesis, which is primarily regulated by the activation of sterol regulatory element-binding protein (SREBP). However, whether SREBP regulation can be targeted for cancer treatment remains unclear. Here, it is demonstrated that treating tumor cells with a peptide that replicates the amino acid sequence in Insig1/2 loop 1, which is the region where Insig1/2 interacts with AKT-phosphorylated phosphoenolpyruvate carboxykinase 1 (PCK1), inhibits the IGF1-induced interaction between PCK1 and Insig1/2. Consequently, this treatment abrogates PCK1-mediated phosphorylation of Insig1 at S207 and Insig2 at S151, reduces the nuclear accumulation of SREBP1, and decreases SREBP1 activity-dependent expression of lipid synthesis genes, lipid accumulation,

SUBMITTER: Luo S 

PROVIDER: S-EPMC12677653 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature