Details

Autor(en) / Beteiligte

• Lee, Ji-Yoon
• Nam, Miso
• Son, Hye Young
• Hyun, Kwangbeom
• Jang, Seo Young
• Kim, Jong Woo
• Kim, Min Wook
• Jung, Youngae
• Jang, Eunji
• Yoon, Seon-Jin
• Kim, Jungeun
• Kim, Jihye
• Seo, Jinho
• Min, Jeong-Ki
• Oh, Kyoung-Jin
• Han, Baek-Soo
• Kim, Won Kon
• Bae, Kwang-Hee
• Song, Jaewhan
• Kim, Jaehoon
• Huh, Yong-Min
• Hwang, Geum-Sook
• Lee, Eun-Woo
• Lee, Sang Chul

Titel

Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2020-12, Vol.117 (51), p.32433-32442

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very longchain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.