Tumor suppressor role of catechol O-methyl transferase in estrogen receptor positive breast cancer through inhibition of cell invasion via MET signaling
| Název česky | Rola katechol-O-methyltransferasy jako tumor supresora u estrogen receptor pozitivního nádoru prsu inhibicí buněčné invaze skrze MET signalizaci |
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| Autoři | |
| Rok publikování | 2021 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Catechol O-methyl transferase (COMT) has been studied as potential tumor-suppressor in breast cancer (BC) due to its involvement in detoxification of catechol estrogens. To understand its potential effect against BC invasion and metastasis, here we examined the effect of COMT overexpression on cell invasion of MCF-7 cell line, a model of luminal A breast cancer subtype, stably transduced with COMT gene (MCF-7 COMT) compared to control cells transduced with empty vector. 2D (transwell) and 3D (spheroid formation) invasion assays showed that COMT overexpression is associated with decreased invasion potential. The cellular-level experiments were complemented by RNA-Seq and proteomics LC-DIA-MS/MS analysis. Gene products associated with cell invasion were downregulated in MCF-7 cells overexpressing COMT while those associated with good prognosis were upregulated at both transcript and protein level. Interestingly, MET signaling as an important target of cancer therapy was found deregulated in proteomic profile, and pulldown analysis identified kunitz-type protease inhibitor 2, SPINT2, involved in negative regulation of c-MET signaling as interaction partner of COMT. We conclude that in addition to involvement in detoxification of catechol estrogens, COMT may act as tumor suppressor by modulation of cell invasion and affecting MET signaling pathway in luminal A breast cancer. |
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