Advanced Science (Jun 2024)

Fatty Acid Oxidation Supports Lymph Node Metastasis of Cervical Cancer via Acetyl‐CoA‐Mediated Stemness

  • Li Yuan,
  • Hongye Jiang,
  • Yan Jia,
  • Yuandong Liao,
  • Caixia Shao,
  • Yijia Zhou,
  • Jiaying Li,
  • Yan Liao,
  • Hua Huang,
  • Yuwen Pan,
  • Weijia Wen,
  • Xueyuan Zhao,
  • Linna Chen,
  • Xu Jing,
  • Chaoyun Pan,
  • Wei Wang,
  • Shuzhong Yao,
  • Chunyu Zhang

DOI
https://doi.org/10.1002/advs.202308422
Journal volume & issue
Vol. 11, no. 21
pp. n/a – n/a

Abstract

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Abstract Accumulating evidence indicates that metabolic reprogramming of cancer cells supports the energy and metabolic demands during tumor metastasis. However, the metabolic alterations underlying lymph node metastasis (LNM) of cervical cancer (CCa) have not been well recognized. In the present study, it is found that lymphatic metastatic CCa cells have reduced dependency on glucose and glycolysis but increased fatty acid oxidation (FAO). Inhibition of carnitine palmitoyl transferase 1A (CPT1A) significantly compromises palmitate‐induced cell stemness. Mechanistically, FAO‐derived acetyl‐CoA enhances H3K27 acetylation (H3K27Ac) modification level in the promoter of stemness genes, increasing stemness and nodal metastasis in the lipid‐rich nodal environment. Genetic and pharmacological loss of CPT1A function markedly suppresses the metastatic colonization of CCa cells in tumor‐draining lymph nodes. Together, these findings propose an effective method of cancer therapy by targeting FAO in patients with CCa and lymph node metastasis.

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