Unique lipid composition maintained by extracellular blockade leads to prooncogenicity

Kai Kudo, Ryo Yanagiya, Masanori Hasegawa, Joaquim Carreras, Yoshimi Miki, Shunya Nakayama, Etsuko Nagashima, Yuji Miyatake, Kan Torii, Kiyoshi Ando, Naoya Nakamura, Akira Miyajima, Makoto Murakami, Ai Kotani

Research output: Contribution to journalArticlepeer-review


Lipid-mediated inflammation is involved in the development and malignancy of cancer. We previously demonstrated the existence of a novel oncogenic mechanism utilizing membrane lipids of extracellular vesicles in Epstein–Barr virus (EBV)-positive lymphomas and found that the lipid composition of lymphoma cells is skewed toward ω-3 fatty acids, which are anti-inflammatory lipids, suggesting an alteration in systemic lipid composition. The results showed that arachidonic acid (AA), an inflammatory lipid, was significantly reduced in the infected cells but detected at high levels in the sera of EBV-positive patients lead to the finding of the blockade of extracellular AA influx by downregulating FATP2, a long-chain fatty acid transporter that mainly transports AA in EBV-infected lymphoma cells. Low AA levels in tumor cells induced by downregulation of FATP2 expression confer resistance to ferroptosis and support tumor growth. TCGA data analysis and xenograft models have demonstrated that the axis plays a critical role in several types of cancers, especially poor prognostic cancers, such as glioblastoma and melanoma. Overall, our in vitro, in vivo, in silico, and clinical data suggest that several cancers exert oncogenic activity by maintaining their special lipid composition via extracellular blockade.

Original languageEnglish
Article number221
JournalCell Death Discovery
Issue number1
Publication statusPublished - Dec 2024


Dive into the research topics of 'Unique lipid composition maintained by extracellular blockade leads to prooncogenicity'. Together they form a unique fingerprint.

Cite this