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Steering tumor progression through the transcriptional response to growth factors and stroma
Author(s) -
Feldman Morris E.,
Yarden Yosef
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.05.036
Subject(s) - biology , suppressor , microrna , gene , phenotype , stroma , microbiology and biotechnology , cell growth , cancer research , apoptosis , genetics , immunology , immunohistochemistry
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.