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

Magdalena Dragan; Mai Uyen Nguyen; Stephania Guzman; Cameron Goertzen; Muriel Brackstone; Waljit S. Dhillo; Paul R. Bech; Sophie Clarke; Ali Abbara; Alan B. Tuck; David A. Hess; Sharon R. Pine; Wei Xing Zong; Frederic E. Wondisford; Xiaoyang Su; Andy V. Babwah; Moshmi Bhattacharya

doi:10.1038/s41419-020-2305-7

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

Magdalena Dragan, Mai Uyen Nguyen, Stephania Guzman, Cameron Goertzen, Muriel Brackstone, Waljit S. Dhillo, Paul R. Bech, Sophie Clarke, Ali Abbara, Alan B. Tuck, David A. Hess, Sharon R. Pine, Wei Xing Zong, Frederic E. Wondisford, Xiaoyang Su, Andy V. Babwah, Moshmi Bhattacharya

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), 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.

Original language	English (US)
Article number	106
Journal	Cell Death and Disease
Volume	11
Issue number	2
DOIs	https://doi.org/10.1038/s41419-020-2305-7
State	Published - Feb 1 2020

All Science Journal Classification (ASJC) codes

Immunology
Cellular and Molecular Neuroscience
Cell Biology
Cancer Research

Access to Document

10.1038/s41419-020-2305-7

Cite this

Dragan, M., Nguyen, M. U., Guzman, S., Goertzen, C., Brackstone, M., Dhillo, W. S., Bech, P. R., Clarke, S., Abbara, A., Tuck, A. B., Hess, D. A., Pine, S. R., Zong, W. X., Wondisford, F. E., Su, X., Babwah, A. V., & Bhattacharya, M. (2020). G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer. Cell Death and Disease, 11(2), Article 106. https://doi.org/10.1038/s41419-020-2305-7

@article{0d74b287fef44e76b3460db65790c204,

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

abstract = "Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), 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.",

author = "Magdalena Dragan and Nguyen, {Mai Uyen} and Stephania Guzman and Cameron Goertzen and Muriel Brackstone and Dhillo, {Waljit S.} and Bech, {Paul R.} and Sophie Clarke and Ali Abbara and Tuck, {Alan B.} and Hess, {David A.} and Pine, {Sharon R.} and Zong, {Wei Xing} and Wondisford, {Frederic E.} and Xiaoyang Su and Babwah, {Andy V.} and Moshmi Bhattacharya",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = feb,

day = "1",

doi = "10.1038/s41419-020-2305-7",

language = "English (US)",

volume = "11",

journal = "Cell Death and Disease",

issn = "2041-4889",

publisher = "Nature Publishing Group",

number = "2",

}

Dragan, M, Nguyen, MU, Guzman, S, Goertzen, C, Brackstone, M, Dhillo, WS, Bech, PR, Clarke, S, Abbara, A, Tuck, AB, Hess, DA, Pine, SR, Zong, WX, Wondisford, FE, Su, X, Babwah, AV & Bhattacharya, M 2020, 'G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer', Cell Death and Disease, vol. 11, no. 2, 106. https://doi.org/10.1038/s41419-020-2305-7

TY - JOUR

T1 - G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer

AU - Dragan, Magdalena

AU - Nguyen, Mai Uyen

AU - Guzman, Stephania

AU - Goertzen, Cameron

AU - Brackstone, Muriel

AU - Dhillo, Waljit S.

AU - Bech, Paul R.

AU - Clarke, Sophie

AU - Abbara, Ali

AU - Tuck, Alan B.

AU - Hess, David A.

AU - Pine, Sharon R.

AU - Zong, Wei Xing

AU - Wondisford, Frederic E.

AU - Su, Xiaoyang

AU - Babwah, Andy V.

AU - Bhattacharya, Moshmi

PY - 2020/2/1

Y1 - 2020/2/1

N2 - Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), 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.

AB - Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), 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.

UR - http://www.scopus.com/inward/record.url?scp=85079080751&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85079080751&partnerID=8YFLogxK

U2 - 10.1038/s41419-020-2305-7

DO - 10.1038/s41419-020-2305-7

M3 - Article

C2 - 32034133

AN - SCOPUS:85079080751

SN - 2041-4889

VL - 11

JO - Cell Death and Disease

JF - Cell Death and Disease

IS - 2

M1 - 106

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this