G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer

被引：13

作者：

Dragan, Magdalena ^{[1
]}

Nguyen, Mai-Uyen ^{[1
]}

Guzman, Stephania ^{[1
]}

Goertzen, Cameron ^{[2
]}

Brackstone, Muriel ^{[3
]}

Dhillo, Waljit S. ^{[4
]}

Bech, Paul R. ^{[4
]}

Clarke, Sophie ^{[4
]}

Abbara, Ali ^{[4
]}

Tuck, Alan B. ^{[5
]}

Hess, David A. ^{[6
]}

Pine, Sharon R. ^{[1
,7
]}

Zong, Wei-Xing ^{[7
,8
]}

Wondisford, Frederic E. ^{[1
,7
,9
]}

Su, Xiaoyang ^{[1
,7
]}

Babwah, Andy V. ^{[9
,10
]}

Bhattacharya, Moshmi ^{[1
,7
,9
]}

机构：

[1] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08901 USA

[2] Univ Toronto, Canc Invas & Metastasis Lab, Fac Dent, Toronto, ON, Canada

[3] London Hlth Sci Ctr, Dept Surg, London, ON, Canada

[4] Imperial Coll London, Sect Invest Med, London, England

[5] Univ Western Ontario, Dept Pathol, London, ON, Canada

[6] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON, Canada

[7] Rutgers State Univ, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA

[8] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Biol Chem, New Brunswick, NJ USA

[9] Child Hlth Inst New Jersey, New Brunswick, NJ 08901 USA

[10] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Pediat, New Brunswick, NJ USA

来源：

CELL DEATH & DISEASE | 2020年 / 11卷 / 02期

基金：

加拿大健康研究院;

关键词：

GLUTAMINE-METABOLISM; TUMOR-SUPPRESSOR; HORMONE-RELEASE; DUAL ROLE; MYC; EXPRESSION; CELL; KISS1; OPPORTUNITIES; METASTASIS;

D O I：

10.1038/s41419-020-2305-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ER alpha), progesterone receptor (PR), and HER2 (ErbB2) and exhibit increased glutamine metabolism, a requirement for tumor growth. The G protein-coupled kisspeptin receptor (KISS1R) is highly expressed in patient TNBC tumors and promotes malignant transformation of breast epithelial cells. This study found that TNBC patients displayed elevated plasma kisspeptin levels compared with healthy subjects. It also provides the first evidence that in addition to promoting tumor growth and metastasis in vivo, KISS1R-induced glutamine dependence of tumors. In addition, tracer-based metabolomics analyses revealed that KISS1R promoted glutaminolysis and nucleotide biosynthesis by increasing c-Myc and glutaminase levels, key regulators of glutamine metabolism. Overall, this study establishes KISS1R as a novel regulator of TNBC metabolism and metastasis, suggesting that targeting KISS1R could have therapeutic potential in the treatment of TNBC.

引用

页数：20

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