IGFBP1 orchestrates metabolic reprogramming to drive clear cell renal cell carcinoma progression through NR1H4-mediated lipid homeostasis disruption.

ABSTRACT: The hallmark lipid accumulation phenotype observed in clear cell renal cell carcinoma (ccRCC) serves as a critical pathophysiological driver of tumor progression. Our investigation revealed that IGFBP1 expression was significantly elevated in ccRCC versus matched normal renal tissues, with increased levels correlating with poorer patient survival outcomes. IGFBP1 knockdown not only suppressed tumor proliferation and invasiveness in vitro but also provoked substantial lipidomic remodeling, as validated through comprehensive lipidomic profiling. Specifically, IGFBP1-deficient cells demonstrated marked reductions in triglycerides (TGs), diacylglycerols (DAGs), free fatty acids (FFA), and cholesterol esters (CEs), thereby establishing IGFBP1 as a key regulator of the metabolic derangements' ch

SUBMITTER: Sun Y 

PROVIDER: S-EPMC12302755 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature