PAX8 and MECOM are interaction partners driving ovarian cancer

Melusine Bleu, Fanny Mermet-Meillon, Verena Apfel, Louise Barys, Laura Holzer, Marianne Bachmann Salvy, Rui Lopes, Inês Amorim Monteiro Barbosa, Cecile Delmas, Alexandra Hinniger, Suzanne Chau, Markus Kaufmann, Simon Haenni, Karolin Berneiser, Maria Wahle, Ivana Moravec, Alexandra Vissières, Tania Poetsch, Erik Ahrné, Nathalie Carte, Johannes Voshol, Elisabeth Bechter, Jacques Hamon, Marco Meyerhofer, Dirk Erdmann, Matteo Fischer, Therese Stachyra, Felix Freuler, Sascha Gutmann, César Fernández, Tobias Schmelzle, Ulrike Naumann, Guglielmo Roma, Kate Lawrenson, Cristina Nieto-Oberhuber, Amanda Cobos-Correa, Stephane Ferretti, Dirk Schübeler and Giorgio Giacomo Galli ()
Additional contact information
Melusine Bleu: Novartis Institutes for Biomedical Research
Fanny Mermet-Meillon: Novartis Institutes for Biomedical Research
Verena Apfel: Novartis Institutes for Biomedical Research
Louise Barys: Novartis Institutes for Biomedical Research
Laura Holzer: Novartis Institutes for Biomedical Research
Marianne Bachmann Salvy: Novartis Institutes for Biomedical Research
Rui Lopes: Novartis Institutes for Biomedical Research
Inês Amorim Monteiro Barbosa: Novartis Institutes for Biomedical Research
Cecile Delmas: Novartis Institutes for Biomedical Research
Alexandra Hinniger: Novartis Institutes for Biomedical Research
Suzanne Chau: Novartis Institutes for Biomedical Research
Markus Kaufmann: Novartis Institutes for Biomedical Research
Simon Haenni: Novartis Institutes for Biomedical Research
Karolin Berneiser: Novartis Institutes for Biomedical Research
Maria Wahle: Novartis Institutes for Biomedical Research
Ivana Moravec: Novartis Institutes for Biomedical Research
Alexandra Vissières: Novartis Institutes for Biomedical Research
Tania Poetsch: Novartis Institutes for Biomedical Research
Erik Ahrné: Novartis Institutes for Biomedical Research
Nathalie Carte: Novartis Institutes for Biomedical Research
Johannes Voshol: Novartis Institutes for Biomedical Research
Elisabeth Bechter: Novartis Institutes for Biomedical Research
Jacques Hamon: Novartis Institutes for Biomedical Research
Marco Meyerhofer: Novartis Institutes for Biomedical Research
Dirk Erdmann: Novartis Institutes for Biomedical Research
Matteo Fischer: Novartis Institutes for Biomedical Research
Therese Stachyra: Novartis Institutes for Biomedical Research
Felix Freuler: Novartis Institutes for Biomedical Research
Sascha Gutmann: Novartis Institutes for Biomedical Research
César Fernández: Novartis Institutes for Biomedical Research
Tobias Schmelzle: Novartis Institutes for Biomedical Research
Ulrike Naumann: Novartis Institutes for Biomedical Research
Guglielmo Roma: Novartis Institutes for Biomedical Research
Kate Lawrenson: Cedars-Sinai Women’s Cancer Program at the Samuel Oschin Cancer Center
Cristina Nieto-Oberhuber: Novartis Institutes for Biomedical Research
Amanda Cobos-Correa: Novartis Institutes for Biomedical Research
Stephane Ferretti: Novartis Institutes for Biomedical Research
Dirk Schübeler: Friedrich Miescher Institute for Biomedical Research, University of Basel
Giorgio Giacomo Galli: Novartis Institutes for Biomedical Research

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract The transcription factor PAX8 is critical for the development of the thyroid and urogenital system. Comprehensive genomic screens furthermore indicate an additional oncogenic role for PAX8 in renal and ovarian cancers. While a plethora of PAX8-regulated genes in different contexts have been proposed, we still lack a mechanistic understanding of how PAX8 engages molecular complexes to drive disease-relevant oncogenic transcriptional programs. Here we show that protein isoforms originating from the MECOM locus form a complex with PAX8. These include MDS1-EVI1 (also called PRDM3) for which we map its interaction with PAX8 in vitro and in vivo. We show that PAX8 binds a large number of genomic sites and forms transcriptional hubs. At a subset of these, PAX8 together with PRDM3 regulates a specific gene expression module involved in adhesion and extracellular matrix. This gene module correlates with PAX8 and MECOM expression in large scale profiling of cell lines, patient-derived xenografts (PDXs) and clinical cases and stratifies gynecological cancer cases with worse prognosis. PRDM3 is amplified in ovarian cancers and we show that the MECOM locus and PAX8 sustain in vivo tumor growth, further supporting that the identified function of the MECOM locus underlies PAX8-driven oncogenic functions in ovarian cancer.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22708-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22708-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-22708-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().