| 論文作者 |
He, DS; Wu, QY; Tian, P; Liu, Y; Jia, ZC; Li, ZW; Wang, Y; Jin, YC; Luo, WQ; Li, L; Zhang, PY; Jin, QL; Zhao, WJ; Hu, WG; Liang, YJ; Zhou, B; Yang, QF; Jiang, YZ; Shao, ZM; Hu, GH |
| 摘要 |
Disseminated tumor cells (DTCs) can remain in a non-proliferative, dormant state for years in distant organs, but the exogenous causes triggering their reactivation and metastatic colonization are unclear. Here, we demonstrate that chemotherapeutic drugs, including doxorubicin and cisplatin, enhance proliferation and lung metastasis of dormant breast cancer cells. Using a recombinase-based dormancy tracing system, DormTracer, we confirm chemotherapy-induced reactivation of dormant DTCs leading to metastatic relapse. Mechanistically, chemotherapy induces fibroblast senescence, which promotes formation of neutrophil extracellulartraps (NETs) through secreted proteins. NETs promote dormant DTC proliferation through extra-cellular matrix remodeling. Importantly, combining senolytic drugs, dasatinib and quercetin, with doxorubicin inhibits post-therapy DTC reactivation and suppresses metastatic relapse. This study provides direct evidence of dormancy awakening and reveals a mechanism underlying detrimental effect of chemotherapy on metastasis, highlighting potential strategies to improve cancer treatment. |
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