Identifying a gene signature of metastatic potential by linking pre-metastatic state to ultimate metastatic fate.

ABSTRACT: Identifying the key molecular pathways that enable metastasis by analyzing the eventual metastatic tumor is challenging because the state of the founder subclone likely changes following metastatic colonization. To address this challenge, we labeled primary mouse pancreatic ductal adenocarcinoma (PDAC) subclones with DNA barcodes to characterize their pre-metastatic state using ATAC-seq and RNA-seq and determine their relative in vivo metastatic potential prospectively. We identified a gene signature separating metastasis-high and metastasis-low subclones orthogonal to the normal-to-PDAC and classical-to-basal axes. The metastasis-high subclones feature activation of IL-1 pathway genes and high NF-κB and Zeb/Snail family activity and the metastasis-low subclones feature activation o

SUBMITTER: Handler JS 

PROVIDER: S-EPMC11343111 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature