Delta-5-desaturase: A novel therapeutic target for cancer management.
Delta-5-desaturase: A novel therapeutic target for cancer management.
复制标题
DOI：
10.1016/j.tranon.2021.101207
复制
发表时间：
2021-11
影响因子：
5
通讯作者：
Qian S
中科院分区：
文献类型：
--
作者：
Pang L;Shah H;Xu Y;Qian S
D5 D是癌症的独立预后因素。D5 D通过介导DGLA产生AA/PGE 2来延缓癌症进展。AA/PGE 2通过调节肿瘤微环境促进肿瘤进展。抑制D5 D重定向考克斯-2催化DGLA过氧化，产生8-HOA。8-HOA通过调节增殖、凋亡和转移来抑制癌症。δ-5去饱和酶（D5 D）是一种限速酶，其将双键引入到n-3和n-6多不饱和脂肪酸链的δ-5位置。由于脂肪酸代谢是癌症发展的重要因素，最近的几项研究表明，D5 D活性和表达可能是癌症的独立预后因素。然而，D5 D在癌症进展中的机制基础仍然存在争议。经典的观点认为，D5 D可通过介导二高-γ-亚麻酸（DGLA）产生花生四烯酸（AA）/前列腺素E2，导致EP受体激活、炎症通路和免疫抑制而加重癌症进展。相反，D5 D可以通过激活铁凋亡（铁依赖性细胞死亡）来预防癌症进展。通过RNA干扰和小分子抑制剂抑制D5 D已被确定为有前途的抗癌策略。抑制D5 D可以将DGLA过氧化模式从产生AA转变为一种独特的抗癌自由基副产物8-羟基辛酸，从而激活细胞凋亡途径，同时抑制癌细胞的生存、增殖、迁移和侵袭。因此，了解D5 D对癌症的分子机制可能有助于开发新的治疗应用。鉴于D5 D可能作为一个有前途的目标在癌症中，在这篇综述中，我们提供了一个更新的总结目前的知识D5 D在癌症发展中的作用和潜在的有用的治疗策略。
D5D is an independent prognostic factor in cancer. D5D aggravates cancer progression via mediating AA/PGE2 production from DGLA. AA/PGE2 promotes cancer progression via regulating the tumor microenvironment. Inhibition of D5D redirects COX-2 catalyzed DGLA peroxidation, producing 8-HOA. 8-HOA suppress cancer by regulating proliferation, apoptosis, and metastasis. Delta-5 desaturase (D5D) is a rate-limiting enzyme that introduces double-bonds to the delta-5 position of the n-3 and n-6 polyunsaturated fatty acid chain. Since fatty acid metabolism is a vital factor in cancer development, several recent studies have revealed that D5D activity and expression could be an independent prognostic factor in cancers. However, the mechanistic basis of D5D in cancer progression is still controversial. The classical concept believes that D5D could aggravate cancer progression via mediating arachidonic acid (AA)/prostaglandin E2 production from dihomo-γ-linolenic acid (DGLA), resulting in activation of EP receptors, inflammatory pathways, and immunosuppression. On the contrary, D5D may prevent cancer progression through activating ferroptosis, which is iron-dependent cell death. Suppression of D5D by RNA interference and small-molecule inhibitor has been identified as a promising anti-cancer strategy. Inhibition of D5D could shift DGLA peroxidation pattern from generating AA to a distinct anti-cancer free radical byproduct, 8-hydroxyoctanoic acid, resulting in activation of apoptosis pathway and simultaneously suppression of cancer cell survival, proliferation, migration, and invasion. Hence, understanding the molecular mechanisms of D5D on cancer may therefore facilitate the development of novel therapeutical applications. Given that D5D may serve as a promising target in cancer, in this review, we provide an updated summary of current knowledge on the role of D5D in cancer development and potentially useful therapeutic strategies.
登录
查看更多内容
ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
5.1
作者：
Athinarayanan S;Fan YY;Wang X;Callaway E;Cai D;Chalasani N;Chapkin RS;Liu W
通讯作者：
Liu W
影响因子：
5.5
作者：
Chen X;Yu C;Kang R;Tang D
通讯作者：
Tang D
DOI：
10.1158/1055-9965.epi-09-0680
发表时间：
2009-11
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Dong LM;Shu XO;Gao YT;Milne G;Ji BT;Yang G;Li HL;Rothman N;Zheng W;Chow WH;Abnet CC
通讯作者：
Abnet CC