Dynamic MAPK signaling activity underlies a transition from growth arrest to proliferation in Drosophila scribble mutant tumors

Disease Models & Mechanisms
Tiantian JiYan Yan

Abstract

Human tumors exhibit plasticity and evolving capacity over time. It is difficult to study the mechanisms of how tumors change over time in human patients, in particular during the early stages when a few oncogenic cells are barely detectable. Here, we used a Drosophila tumor model caused by loss of scribble (scrib), a highly conserved apicobasal cell polarity gene, to investigate the spatial-temporal dynamics of early tumorigenesis events. The fly scrib mutant tumors have been successfully used to model many aspects of tumorigenesis processes. However, it is still unknown whether Drosophila scrib mutant tumors exhibit plasticity and evolvability along the temporal axis. We found that scrib mutant tumors displayed different growth rates and cell cycle profiles over time, indicative of a growth arrest-to-proliferation transition as the scrib mutant tumors progress. Longitudinal bulk and single-cell transcriptomic analysis of scrib mutant tumors revealed that the MAPK pathway, including JNK and ERK signaling activities, showed quantitative changes over time. We found that high JNK signaling activity caused G2/M cell cycle arrest in early scrib mutant tumors. In addition, JNK signaling activity displayed a radial polarity with the ...Continue Reading

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Citations

Jul 18, 2020·Cancer Science·Hiroshi Kanda, Tatsushi Igaki
Sep 18, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Hongjie Li
Mar 3, 2020·Frontiers in Cell and Developmental Biology·John E La Marca, Helena E Richardson
Nov 18, 2020·Journal of Cell Science·Kenneth Kin Lam WongEsther M Verheyen
Jul 10, 2021·Disease Models & Mechanisms·Kenneth Kin Lam Wong, Esther M Verheyen

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Datasets Mentioned

BETA
GSE130243
GSE130566

Methods Mentioned

BETA
FACS
flow cytometry
PCA
RNA-seq
protein-trap
dissection

Software Mentioned

FlowJo
STAR
Fiji
clusterProfiler
DEseq2
Seurat
edgeR
Subread
R
featureCounts

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