The matrix protein Fibulin-3 promotes KISS1R induced triple negative breast cancer cell invasion
| Autor: | Michael M Mehta, Andy V. Babwah, Moshmi Bhattacharya, Navin Viswakarma, Magdalena Dragan, Frederic E. Wondisford, Ajay Rana, Alan B. Tuck, Michelle M Noonan, David A. Hess, Muriel Brackstone |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway medicine.medical_treatment Kisspeptin receptor Estrogen receptor Metastasis Targeted therapy 03 medical and health sciences 0302 clinical medicine Breast cancer Invasion Triple-negative breast cancer Progesterone receptor metastasis Medicine kisspeptin receptor business.industry Fibulin-3 invasion medicine.disease 3. Good health Fibulin 030104 developmental biology Oncology 030220 oncology & carcinogenesis triple-negative breast cancer Cancer research fibulin-3 business Research Paper |
| Zdroj: | Paediatrics Publications Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.25682 |
| Popis: | Breast cancer is a leading cause of cancer mortality. In particular, triple negative breast cancer (TNBC) comprise a heterogeneous group of basal-like tumors lacking estrogen receptor (ERα), progesterone receptor (PR) and HER2 (ErbB2). TNBC represents 15-20% of all breast cancers and occurs frequently in women under 50 years of age. Unfortunately, these patients lack targeted therapy, are typically high grade and metastatic at time of diagnosis. The mechanisms regulating metastasis remain poorly understood. We have previously shown that the kisspeptin receptor, KISS1R stimulates invasiveness of TNBC cells. In this report, we demonstrate that KISS1R signals via the secreted extracellular matrix protein, fibulin-3, to regulate TNBC invasion. We found that the fibulin-3 gene is amplified in TNBC primary tumors and that plasma fibulin-3 levels are elevated in TNBC patients compared to healthy subjects. In this study, we show that KISS1R activation increases fibulin-3 expression and secretion. We show that fibulin-3 regulates TNBC metastasis in a mouse experimental metastasis xenograft model and signals downstream of KISS1R to stimulate TNBC invasion, by activating matrix metalloproteinase 9 (MMP-9) and the MAPK pathway. These results identify fibulin-3 as a new downstream mediator of KISS1R signaling and as a potential biomarker for TNBC progression and metastasis, thus revealing KISS1R and fibulin-3 as novel drug targets in TNBC. |
| Databáze: | OpenAIRE |
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