Identification of phenotype-specific networks from paired gene expression-cell shape imaging data.
Date
2022-04-01ICR Author
Author
Barker, CG
Petsalaki, E
Giudice, G
Sero, J
Ekpenyong, EN
Bakal, C
Petsalaki, E
Type
Journal Article
Metadata
Show full item recordAbstract
The morphology of breast cancer cells is often used as an indicator of tumor severity and prognosis. Additionally, morphology can be used to identify more fine-grained, molecular developments within a cancer cell, such as transcriptomic changes and signaling pathway activity. Delineating the interface between morphology and signaling is important to understand the mechanical cues that a cell processes in order to undergo epithelial-to-mesenchymal transition and consequently metastasize. However, the exact regulatory systems that define these changes remain poorly characterized. In this study, we used a network-systems approach to integrate imaging data and RNA-seq expression data. Our workflow allowed the discovery of unbiased and context-specific gene expression signatures and cell signaling subnetworks relevant to the regulation of cell shape, rather than focusing on the identification of previously known, but not always representative, pathways. By constructing a cell-shape signaling network from shape-correlated gene expression modules and their upstream regulators, we found central roles for developmental pathways such as WNT and Notch, as well as evidence for the fine control of NF-kB signaling by numerous kinase and transcriptional regulators. Further analysis of our network implicates a gene expression module enriched in the RAP1 signaling pathway as a mediator between the sensing of mechanical stimuli and regulation of NF-kB activity, with specific relevance to cell shape in breast cancer.
Collections
Subject
Breast Neoplasms
Cell Shape
Female
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
NF-kappa B
Phenotype
Transcriptome
Research team
Dynamical Cell Systems
Language
eng
Date accepted
2022-02-17
License start date
2022-04-01
Citation
Genome Research, 2022, 32 (4), pp. 750 - 765
Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT