Near-Death Cells Cause Chemotherapy-Induced Metastasis via ATF4-Mediated NF-κB Signaling Activation.

ABSTRACT: Cytotoxic chemotherapy is a primary treatment modality for many patients with advanced cancer. Increasing preclinical and clinical observations indicate that chemotherapy can exacerbate tumor metastasis. However, the underlying mechanism remains unclear. Here, it is attempted to identify the mechanisms underlying chemotherapy-induced cancer recurrence and metastasis. It is revealed that a small subpopulation of "near-death cells" (NDCs) with compromised plasma membranes can reverse the death process to enhance survival and repopulation after exposure to lethal doses of cytotoxins. Moreover, these NDCs acquire enhanced tumorigenic and metastatic capabilities, but maintain chemosensitivity in multiple models. Mechanistically, cytotoxin exposure induces activating transcription factor 4 (ATF4

SUBMITTER: Zhu C 

PROVIDER: S-EPMC10074103 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature