0 70

Cited 0 times in

Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer

Authors
 Ji-Yoon Lee  ;  Miso Nam  ;  Hye Young Son  ;  Kwangbeom Hyun  ;  Seo Young Jang  ;  Jong Woo Kim  ;  Min Wook Kim  ;  Youngae Jung  ;  Eunji Jang  ;  Seon-Jin Yoon  ;  Jungeun Kim  ;  Jihye Kim  ;  Jinho Seo  ;  Jeong-Ki Min  ;  Kyoung-Jin Oh  ;  Baek-Soo Han  ;  Won Kon Kim  ;  Kwang-Hee Bae  ;  Jaewhan Song  ;  Jaehoon Kim  ;  Yong-Min Huh  ;  Geum-Sook Hwang  ;  Eun-Woo Lee  ;  Sang Chul Lee 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.117(51) : 32433-32442, 2020-12 
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN
 0027-8424 
Issue Date
2020-12
MeSH
Arachidonic Acid / genetics ; Arachidonic Acid / metabolism ; Arachidonic Acid / pharmacology ; Carbolines / pharmacology ; Cell Line, Tumor ; DNA Methylation ; Enhancer Elements, Genetic ; Fatty Acid Desaturases / genetics ; Fatty Acid Desaturases / metabolism ; Fatty Acid Elongases / genetics ; Fatty Acid Elongases / metabolism ; Fatty Acids, Unsaturated / biosynthesis* ; Fatty Acids, Unsaturated / genetics ; Fatty Acids, Unsaturated / metabolism ; Ferroptosis / drug effects ; Ferroptosis / genetics ; Ferroptosis / physiology* ; Gene Expression Regulation, Neoplastic ; Humans ; Lipid Metabolism / genetics ; Promoter Regions, Genetic ; Stomach Neoplasms / drug therapy ; Stomach Neoplasms / genetics* ; Stomach Neoplasms / metabolism* ; Stomach Neoplasms / pathology
Keywords
ELOVL5 ; FADS1 ; arachidonic acid ; ferroptosis ; lipid peroxidation
Abstract
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 long-chain 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.
Full Text
https://www.pnas.org/content/117/51/32433.long
DOI
10.1073/pnas.2006828117
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Son, Hye Yeong(손혜영) ORCID logo https://orcid.org/0000-0001-5977-6784
Yoon, Seon Jin(윤선진) ORCID logo https://orcid.org/0000-0002-3255-5081
Huh, Yong Min(허용민) ORCID logo https://orcid.org/0000-0002-9831-4475
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182566
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links