ERF mutations reveal a balance of ETS factors controlling prostate oncogenesis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-06

AUTHORS

Rohit Bose, Wouter R. Karthaus, Joshua Armenia, Wassim Abida, Phillip J. Iaquinta, Zeda Zhang, John Wongvipat, Elizabeth V. Wasmuth, Neel Shah, Patrick S. Sullivan, Michael G. Doran, Ping Wang, Anna Patruno, Yilin Zhao, The International SU2C/PCF Prostate Cancer Dream Team, Dan Robinson, Eliezer M. Van Allen, Yi-Mi Wu, Nikolaus Schultz, Robert J. Lonigro, Juan-Miguel Mosquera, Bruce Montgomery, Mary-Ellen Taplin, Colin C. Pritchard, Gerhardt Attard, Himisha Beltran, Robert K. Bradley, Jake Vinson, Xuhong Cao, Pankaj Vats, Lakshmi P. Kunju, Maha Hussain, Scott A. Tomlins, Kathleen A. Cooney, David C. Smith, Christine Brennan, Javed Siddiqui, Rohit Mehra, Yu Chen, Dana E. Rathkopf, Michael J. Morris, Stephen B. Solomon, Jeremy C. Durack, Victor E. Reuter, Anuradha Gopalan, Jianjiong Gao, Massimo Loda, Rosina T. Lis, Michaela Bowden, Stephen P. Balk, Glenn Gaviola, Carrie Sougnez, Manaswi Gupta, Evan Y. Yu, Elahe A. Mostaghel, Heather H. Cheng, Hyojeong Mulcahy, Lawrence D. True, Stephen R. Plymate, Heidi Dvinge, Roberta Ferraldeschi, Penny Flohr, Susana Miranda, Zafeiris Zafeiriou, Nina Tunariu, Joaquin Mateo, Raquel Perez-Lopez, Francesca Demichelis, Brian D. Robinson, Marc Schiffman, David M. Nanus, Scott T. Tagawa, Alexandros Sigaras, Kenneth W. Eng, Olivier Elemento, Andrea Sboner, Elisabeth I. Heath, Howard I. Scher, Kenneth J. Pienta, Philip Kantoff, Johann S. de Bono, Mark A. Rubin, Peter S. Nelson, Levi A. Garraway, Charles L. Sawyers, Arul M. Chinnaiyan, Deyou Zheng

ABSTRACT

Half of all prostate cancers are caused by the TMPRSS2-ERG gene-fusion, which enables androgens to drive expression of the normally silent E26 transformation-specific (ETS) transcription factor ERG in prostate cells. Recent genomic landscape studies of such cancers have reported recurrent point mutations and focal deletions of another ETS member, the ETS2 repressor factor ERF. Here we show these ERF mutations cause decreased protein stability and mostly occur in tumours without ERG upregulation. ERF loss recapitulates the morphological and phenotypic features of ERG gain in normal mouse prostate cells, including expansion of the androgen receptor transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of Pten loss that yields oncogenic activity by ERG. In the more common scenario of ERG upregulation, chromatin immunoprecipitation followed by sequencing indicates that ERG inhibits the ability of ERF to bind DNA at consensus ETS sites both in normal and in cancerous prostate cells. Consistent with a competition model, ERF overexpression blocks ERG-dependent tumour growth, and ERF loss rescues TMPRSS2-ERG-positive prostate cancer cells from ERG dependency. Collectively, these data provide evidence that the oncogenicity of ERG is mediated, in part, by competition with ERF and they raise the larger question of whether other gain-of-function oncogenic transcription factors might also inactivate endogenous tumour suppressors. More... »

PAGES

671

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature22820

DOI

http://dx.doi.org/10.1038/nature22820

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1086019975

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28614298


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature22820'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature22820'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature22820'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature22820'


 

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