癌症研究
淋巴管新生
脂肪酸合酶
医学
转移
菱形
脂质代谢
癌症
生物
内科学
信号转导
细胞生物学
罗亚
作者
Qiqiao Du,Pan Liu,Chunyu Zhang,Tianyu Li,Wei Wang,Chunliang Shang,Jing‐Ming Wu,Yuandong Liao,Yili Chen,Jiaming Huang,Hao Tan,Yunhe Zhao,Meng Xia,Junxiu Liu,Shuzhong Yao
标识
DOI:10.1038/s41419-022-04926-2
摘要
Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. Clarification of the detailed mechanisms underlying LNM may provide potential clinical therapeutic targets for CC patients with LNM. However, the molecular mechanism of LNM in CC is unclear. In the present study, we demonstrated that fatty acid synthase (FASN), one of the key enzymes in lipid metabolism, had upregulated expression in the CC samples and was correlated with LNM. Moreover, multivariate Cox proportional hazards analysis identified FASN as an independent prognostic factor of CC patients. Furthermore, gain-of-function and loss-of-function approaches showed that FASN promoted CC cell migration, invasion, and lymphangiogenesis. Mechanistically, on the one hand, FASN could regulate cholesterol reprogramming and then activate the lipid raft-related c-Src/AKT/FAK signaling pathway, leading to enhanced cell migration and invasion. On the other hand, FASN induced lymphangiogenesis by secreting PDGF-AA/IGFBP3. More importantly, knockdown of FASN with FASN shRNA or the inhibitors C75 and Cerulenin dramatically diminished LNM in vivo, suggesting that FASN plays an essential role in LNM of CC and the clinical application potential of FASN inhibitors. Taken together, our findings uncover a novel molecular mechanism in LNM of CC and identify FASN as a novel prognostic factor and potential therapeutic target for LNM in CC.
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