Steering Tumor Progression Through the Transcriptional Response to Growth Factors and Stroma
Overview
Authors
Affiliations
Tumor progression can be understood as a collaborative effort of mutations and growth factors, which propels cell proliferation and matrix invasion, and also enables evasion of drug-induced apoptosis. Concentrating on EGFR, we discuss downstream signaling and the initiation of transcriptional events in response to growth factors. Specifically, we portray a wave-like program, which initiates by rapid disappearance of two-dozen microRNAs, followed by an abrupt rise of immediate early genes (IEGs), relatively short transcripts encoding transcriptional regulators. Concurrent with the fall of IEGs, some 30-60 min after stimulation, a larger group, the delayed early genes, is up-regulated and its own fall overlaps the rise of the final wave of late response genes. This late wave persists and determines long-term phenotype acquisition, such as invasiveness. Key regulatory steps in the orderly response to growth factors provide a trove of potential oncogenes and tumor suppressors.
Uribe M, Dahlhoff M, Batra R, Nataraj N, Haga Y, Drago-Garcia D Sci Signal. 2021; 14(688).
PMID: 34158398 PMC: 7614343. DOI: 10.1126/scisignal.abe6156.
Butler J, Barham B, Heidenreich B J Anat. 2019; 234(6):936-942.
PMID: 30861576 PMC: 6539692. DOI: 10.1111/joa.12967.
A Proteomics Approach to Profiling the Temporal Translational Response to Stress and Growth.
Rothenberg D, Taliaferro J, Huber S, Begley T, Dedon P, White F iScience. 2018; 9:367-381.
PMID: 30466063 PMC: 6249402. DOI: 10.1016/j.isci.2018.11.004.
Wang Y, Lee H, Hung M J Biomed Sci. 2018; 25(1):83.
PMID: 30449278 PMC: 6241042. DOI: 10.1186/s12929-018-0484-7.
An immediate-late gene expression module decodes ERK signal duration.
Uhlitz F, Sieber A, Wyler E, Fritsche-Guenther R, Meisig J, Landthaler M Mol Syst Biol. 2017; 13(5):928.
PMID: 28468958 PMC: 5448165. DOI: 10.15252/msb.20177554.