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P63/p73 maintain cancer stem cells in a quasi-mesenchymal state and drive metastatic colonization via EGFR signaling

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE172407 | GEO | 2022/11/22

REPOSITORIES: GEO

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p63/p73 maintain cancer stem cells in a quasi-mesenchymal state and drive metastatic colonization via EGFR signaling [ATAC-Seq]

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p63/p73 maintain cancer stem cells in a quasi-mesenchymal state and drive metastatic colonization via EGFR signaling [ChIP-Seq]

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ΔNp63/p73 drive metastatic colonization by controlling a regenerative epithelial stem cell program in quasi-mesenchymal cancer stem cells.

Project description:Cancer stem cells (CSCs) may serve as the cellular seeds of tumor recurrence and metastasis, and they can be generated via epithelial-mesenchymal transitions (EMTs). Isolating pure populations of CSCs is difficult because EMT programs generate multiple alternative cell states, and phenotypic plasticity permits frequent interconversions between these states. Here, we used cell-surface expression of integrin β4 (ITGB4) to isolate highly enriched populations of human breast CSCs, and we identified the gene regulatory network operating in ITGB4+ CSCs. Specifically, we identified ΔNp63 and p73, the latter of which transactivates ΔNp63, as centrally important transcriptional regulators of quasi-mesenchymal CSCs that reside in an intermediate EMT state. We found that the transcriptional program controlled by ΔNp63 in CSCs is largely distinct from the one that it orchestrates in normal basal mammary stem cells and, instead, it more closely resembles a regenerative epithelial stem cell response to wounding. Moreover, quasi-mesenchymal CSCs repurpose this program to drive metastatic colonization via autocrine EGFR signaling.

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ΔNp63/p73 drive metastatic colonization by controlling a regenerative epithelial stem cell program in quasi-mesenchymal cancer stem cells

Project description:p63/p73 are master transcriptional regulators of ITGB4-hi cancer stem cells and are required to maintain CSCs in a quasi-mesenchymal state and for metastatic colonization

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