| Autor: |
Martina Troiani, Manuel Colucci, Mariantonietta D’Ambrosio, Ilaria Guccini, Emiliano Pasquini, Angelica Varesi, Aurora Valdata, Simone Mosole, Ajinkya Revandkar, Giuseppe Attanasio, Andrea Rinaldi, Anna Rinaldi, Marco Bolis, Pietro Cippà, Andrea Alimonti |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 13, Iss 1, Pp 1-14 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-022-29824-1 |
| Popis: |
Abstract Cells subjected to treatment with anti-cancer therapies can evade apoptosis through cellular senescence. Persistent senescent tumor cells remain metabolically active, possess a secretory phenotype, and can promote tumor proliferation and metastatic dissemination. Removal of senescent tumor cells (senolytic therapy) has therefore emerged as a promising therapeutic strategy. Here, using single-cell RNA-sequencing, we find that senescent tumor cells rely on the anti-apoptotic gene Mcl-1 for their survival. Mcl-1 is upregulated in senescent tumor cells, including cells expressing low levels of Bcl-2, an established target for senolytic therapy. While treatment with the Bcl-2 inhibitor Navitoclax results in the reduction of metastases in tumor bearing mice, treatment with the Mcl-1 inhibitor S63845 leads to complete elimination of senescent tumor cells and metastases. These findings provide insights on the mechanism by which senescent tumor cells survive and reveal a vulnerability that can be exploited for cancer therapy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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