G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer
| Autor: | Mai Uyen Nguyen, Ali Abbara, Muriel Brackstone, Paul Bech, Wei-Xing Zong, Andy V. Babwah, Sharon R. Pine, Sophie A Clarke, Stephania Guzman, Frederic E. Wondisford, Waljit S. Dhillo, David A. Hess, Cameron Goertzen, Xiaoyang Su, Magdalena Dragan, Alan B. Tuck, Moshmi Bhattacharya |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Carcinogenesis Glutamine Estrogen receptor Triple Negative Breast Neoplasms Mice SCID 0601 Biochemistry and Cell Biology medicine.disease_cause Metastasis Malignant transformation Breast cancer 0302 clinical medicine Kisspeptin Cell Movement Mice Inbred NOD 0303 health sciences lcsh:Cytology Nucleotides Middle Aged Cellular Reprogramming Cancer metabolism Tumor Burden 3. Good health Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Female Signal Transduction Adult Immunology Biology Article Proto-Oncogene Proteins c-myc Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience Glutaminase Cell Line Tumor Progesterone receptor medicine Animals Humans Neoplasm Invasiveness 1112 Oncology and Carcinogenesis lcsh:QH573-671 Aged Cell Proliferation 030304 developmental biology Glutaminolysis Cell Biology medicine.disease Case-Control Studies Cancer research Energy Metabolism Receptors Kisspeptin-1 |
| Zdroj: | Paediatrics Publications Cell Death & Disease Cell Death and Disease, Vol 11, Iss 2, Pp 1-20 (2020) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-020-2305-7 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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