Targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells

被引：75

作者：

Chen, Rain R. ^{[1
,2
]}

Yung, Mingo M. H. ^{[1
,2
]}

Xuan, Yang ^{[1
]}

Zhan, Shijie ^{[1
]}

Leung, Leanne L. ^{[1
,2
]}

Liang, Rachel R. ^{[1
,2
]}

Leung, Thomas H. Y. ^{[2
]}

Yang, Huijuan ^{[3
]}

Xu, Dakang ^{[4
]}

Sharma, Rakesh ^{[5
]}

Chan, Karen K. L. ^{[2
]}

Ngu, Siew-Fei ^{[2
]}

Ngan, Hextan Y. S. ^{[1
,2
]}

Chan, David W. ^{[1
,2
]}

机构：

[1] Univ Hong Kong, Shenzhen Inst Res & Innovat HKU SIRI, Shenzhen, Peoples R China

[2] Univ Hong Kong, LKS Fac Med, Dept Obstet & Gynaecol, Hong Kong, Peoples R China

[3] Fudan Univ, Shanghai Canc Ctr, Dept Gynecol Oncol, Shanghai 200032, Peoples R China

[4] Shanghai Jiao Tong Univ, Ruijin Hosp, Fac Med Lab Sci, Sch Med, Shanghai 200030, Peoples R China

[5] Univ Hong Kong, LKS Fac Med, Prote & Metabol Core Facil, Hong Kong, Peoples R China

来源：

COMMUNICATIONS BIOLOGY | 2019年 / 2卷 / 1期

基金：

中国国家自然科学基金;

关键词：

FATTY-ACID SYNTHASE; PROTEIN-KINASE; TUMOR-GROWTH; AMPK; ENERGY; HETEROGENEITY; COLONIZATION; PROGRESSION; ACTIVATION; MIGRATION;

D O I：

10.1038/s42003-019-0508-1

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Ovarian cancer is an intra-abdominal tumor in which the presence of ascites facilitates metastatic dissemination, and associated with poor prognosis. However, the significance of metabolic alterations in ovarian cancer cells in the ascites microenvironment remains unclear. Here we show ovarian cancer cells exhibited increased aggressiveness in ascites microenvironment via reprogramming of lipid metabolism. High lipid metabolic activities are found in ovarian cancer cells when cultured in the ascites microenvironment, indicating a metabolic shift from aerobic glycolysis to beta-oxidation and lipogenesis. The reduced AMP-activated protein kinase (AMPK) activity due to the feedback effect of high energy production led to the activation of its downstream signaling, which in turn, enhanced the cancer growth. The combined treatment of low toxic AMPK activators, the transforming growth factor beta-activated kinase 1 (TAK1) and fatty acid synthase (FASN) inhibitors synergistically impair oncogenic augmentation of ovarian cancer. Collectively, targeting lipid metabolism signaling axis impede ovarian cancer peritoneal metastases.

引用

页数：15

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