Yanning Sun, Yuhu Hao, Fan Peng, Hongju Ling, Kai Sun, Jiechuan Qiu, Tianmin Yang, Leizuo Zhao, Qinghua Xia
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引用次数: 0
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' characteristic of ccRCC pathogenesis. Mechanistic exploration identified NR1H4 as a potential transcriptional regulator operating downstream of IGFBP1-mediated signaling pathways. A thorough interrogation of these pathways established mechanistic links between IGFBP1 activity and endoplasmic reticulum stress, revealing an integrated network that coordinates lipid homeostasis within malignant renal epithelium. These findings substantiated the role of IGFBP1 as a central node in the metabolic reprogramming associated with ccRCC and propose actionable targets for therapeutic intervention through modulation of lipid metabolic pathways.
期刊介绍:
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.