In:
Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-04-21)
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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-022-29824-1
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2553671-0