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Awakening and Eliminating Dormant Cancer Cells: A Foundation for Resistance Removal and Recurrence-Free Recovery [ATAC-seq]

ABSTRACT: Tumor therapy mainly targets the tumor bulk, but tends to fail to eradicate the small resistant population of dormant cancer cells (DCCs) that enable relapse and/or metastasis beyond therapy. Using chemoradiotherapy resistant assay and SETD4 expression of a histone lysine methyltransferase, DCCs with high capacity of tumor-initiation and tumorsphere formation were isolated from three types of breast tumors. Exogenous DEK, a nuclear protein, activated the DCCs by binding to open chromatin which decreased SETD4, up-regulated the MYC and down-regulated the P53 signaling pathways. DEK-containing exosomes in blood highly correlate with tumor progress and exosomal DEK promotes tumor relapse and metastasis beyond chemoradiotherapy. Beyond activation, these formerly dormant cancer cells lost their chemoradiotherapy resistance. In treatment of DEK-containing exosomes plus chemoradiotherapy in mice, three types of breast tumors were eliminated without recurrence. Prior DCCs reactivation, as triggered by exogenous DEK may provide treatment options that eliminate both metastasis and recurrence potential.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164426 | GEO | 2024/01/07

REPOSITORIES: GEO

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