Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer‐associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p‐ACLY axis

• DOI: 10.1111/cas.16111
• Publication Date: 2024-03-18T04:49:59Z
• Authors: Pan Liu; Yue Wang; Xiang Li; Zhenan Liu; Yunqing Sun; Hanzhe Liu; Zhe Shao; Erhui Jiang; Xiaocheng Zhou; Zhengjun Shang
• Keywords: ATP citrate lyase; Interleukin 8; Lipid droplet; Tumor progression

Abstract Lipid metabolic reprogramming of tumor cells has been proven to play a critical role in initiation and development. However, lipid metabolism cancer‐associated fibroblasts (CAFs) rarely studied, particularly CAFs oral squamous cell carcinoma (OSCC). Additionally, the molecular mechanism by which regulate is unclear. In this study, we found that phosphorylated ATP citrate lyase (p‐ACLY), key enzyme, was upregulated OSCC CAFs. Compared paracancerous normal fibroblasts, showed enhanced synthesis, such as elevated cytosolic acetyl‐CoA level accumulation droplets. Conversely, reduction p‐ACLY blocked biological process. addition, blocking synthesis or inhibiting fatty acid uptake reduced promotive effects on proliferation, invasion, migration. These findings suggested are one sources required for progression. Mechanistically, AKT signaling activation involved upregulation Interleukin‐8 (IL8), an exocrine cytokine cells, could activate then phosphorylate ACLY fibroblasts. This study IL8/AKT/p‐ACLY axis be considered potential target treatment.