Signalling crosstalk during early tumorigenesis in the absence of Polycomb silencing.

Abstract:

:In response to stress and injury a coordinated activation of conserved signalling modules, such as JNK and JAK/STAT, is critical to trigger regenerative tissue restoration. While these pathways rebuild homeostasis and promote faithful organ recovery, it is intriguing that they also become activated in various tumour conditions. Therefore, it is crucial to understand how similar pathways can achieve context-dependent functional outputs, likely depending on cellular states. Compromised chromatin regulation, upon removal of the Polycomb group member polyhomeotic, leads to tumour formation with ectopic activation of JNK signalling, mediated by egr/grnd, in addition to JAK/STAT and Notch. Employing quantitative analyses, we show that blocking ectopic signalling impairs ph tumour growth. Furthermore, JAK/STAT functions in parallel to JNK, while Notch relies on JNK. Here, we reveal a signalling hierarchy in ph tumours that is distinct from the regenerative processes regulated by these pathways. Absence of ph renders a permissive state for expression of target genes, but our results suggest that both loss of repression and the presence of activators may collectively regulate gene expression during tumorigenesis. Further dissecting the effect of signalling, developmental or stress-induced factors will thus elucidate the regulation of physiological responses and the contribution of context-specific cellular states.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Beira JV,Torres J,Paro R

doi

10.1371/journal.pgen.1007187

subject

Has Abstract

pub_date

2018-01-22 00:00:00

pages

e1007187

issue

1

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-17-02301

journal_volume

14

pub_type

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