Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I

Dass, Randall A. ; Sarshad, Aishe A. ; Carson, Brittany B. ; Feenstra, Jennifer M. ; Kaur, Amanpreet ; Obrdlik, Ales ; Parks, Matthew M. ; Prakash, Varsha ; Love, Damon K. and Pietras, Kristian LU orcid , et al. (2016) In PLoS Genetics 12(8).
Abstract

Ribosome biogenesis is essential for cell growth and proliferation and is commonly elevated in cancer. Accordingly, numerous oncogene and tumor suppressor signaling pathways target rRNA synthesis. In breast cancer, non-canonical Wnt signaling by Wnt5a has been reported to antagonize tumor growth. Here, we show that Wnt5a rapidly represses rDNA gene transcription in breast cancer cells and generates a chromatin state with reduced transcription of rDNA by RNA polymerase I (Pol I). These effects were specifically dependent on Dishevelled1 (DVL1), which accumulates in nucleolar organizer regions (NORs) and binds to rDNA regions of the chromosome. Upon DVL1 binding, the Pol I transcription activator and deacetylase Sirtuin 7 (SIRT7) releases... (More)

Ribosome biogenesis is essential for cell growth and proliferation and is commonly elevated in cancer. Accordingly, numerous oncogene and tumor suppressor signaling pathways target rRNA synthesis. In breast cancer, non-canonical Wnt signaling by Wnt5a has been reported to antagonize tumor growth. Here, we show that Wnt5a rapidly represses rDNA gene transcription in breast cancer cells and generates a chromatin state with reduced transcription of rDNA by RNA polymerase I (Pol I). These effects were specifically dependent on Dishevelled1 (DVL1), which accumulates in nucleolar organizer regions (NORs) and binds to rDNA regions of the chromosome. Upon DVL1 binding, the Pol I transcription activator and deacetylase Sirtuin 7 (SIRT7) releases from rDNA loci, concomitant with disassembly of Pol I transcription machinery at the rDNA promoter. These findings reveal that Wnt5a signals through DVL1 to suppress rRNA transcription. This provides a novel mechanism for how Wnt5a exerts tumor suppressive effects and why disruption of Wnt5a signaling enhances mammary tumor growth in vivo.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Genetics
volume
12
issue
8
article number
e1006217
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:27500936
  • wos:000382394500023
  • scopus:84984914891
ISSN
1553-7390
DOI
10.1371/journal.pgen.1006217
language
English
LU publication?
yes
id
81766afc-f10e-425a-9fa2-1e99def3fe9a
date added to LUP
2016-10-04 08:37:03
date last changed
2025-01-12 12:34:23
@article{81766afc-f10e-425a-9fa2-1e99def3fe9a,
  abstract     = {{<p>Ribosome biogenesis is essential for cell growth and proliferation and is commonly elevated in cancer. Accordingly, numerous oncogene and tumor suppressor signaling pathways target rRNA synthesis. In breast cancer, non-canonical Wnt signaling by Wnt5a has been reported to antagonize tumor growth. Here, we show that Wnt5a rapidly represses rDNA gene transcription in breast cancer cells and generates a chromatin state with reduced transcription of rDNA by RNA polymerase I (Pol I). These effects were specifically dependent on Dishevelled1 (DVL1), which accumulates in nucleolar organizer regions (NORs) and binds to rDNA regions of the chromosome. Upon DVL1 binding, the Pol I transcription activator and deacetylase Sirtuin 7 (SIRT7) releases from rDNA loci, concomitant with disassembly of Pol I transcription machinery at the rDNA promoter. These findings reveal that Wnt5a signals through DVL1 to suppress rRNA transcription. This provides a novel mechanism for how Wnt5a exerts tumor suppressive effects and why disruption of Wnt5a signaling enhances mammary tumor growth in vivo.</p>}},
  author       = {{Dass, Randall A. and Sarshad, Aishe A. and Carson, Brittany B. and Feenstra, Jennifer M. and Kaur, Amanpreet and Obrdlik, Ales and Parks, Matthew M. and Prakash, Varsha and Love, Damon K. and Pietras, Kristian and Serra, Rosa and Blanchard, Scott C. and Percipalle, Piergiorgio and Brown, Anthony M C and Vincent, C. Theresa}},
  issn         = {{1553-7390}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Genetics}},
  title        = {{Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I}},
  url          = {{http://dx.doi.org/10.1371/journal.pgen.1006217}},
  doi          = {{10.1371/journal.pgen.1006217}},
  volume       = {{12}},
  year         = {{2016}},
}