摘要：SummaryCellular senescence acts as a potent tumor-suppression mechanism in mammals; however, it also promotes tumor progression in a non-cell-autonomous manner. We provided insights into the mechanism underlying senescence-dependent metastatic cancer development. The elimination of senescent cells suppressed the lung metastasis of melanoma cells. Using an antibody array screening of humoral factor(s) that depend on cellular senescence, we identified soluble E-cadherin (seCad) as a potential mediator of the senescence-induced melanoma metastasis. seCad enhanced the invasive activity of melanoma cells bothin vitroandin vivo, and gene expression profiling revealed that seCad induced genes associated with poor prognosis in patients with melanoma. An analysis of sera from patients revealed that serum seCad is associated with distant metastasis. Our data suggest that senescent cells promote metastatic lung cancer through seCad, and that seCad may be a potential diagnostic marker as well as a therapeutic target for metastatic lung cancer.Graphical abstractDisplay OmittedHighlights•Elimination of senescent cells diminished lung metastasis of B16-F10 melanoma cells•Senescent cells enhanced ectodomain shedding of the E-cadherin protein•The resultant soluble E-cadherin (seCad) promotes lung metastasis•Plasma seCad level is associated with metastasis in patients with melanomaCell biology; Cancer
