MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas

Tina Gruosso, Camille Garnier, Sophie Abelanet, Yann Kieffer, Vincent Lemesre, Dorine Bellanger, Ivan Bieche, Elisabetta Marangoni, Xavier Sastre-Garau, Virginie Mieulet () and Fatima Mechta-Grigoriou ()
Additional contact information
Tina Gruosso: Stress and Cancer Laboratory, Institut Curie
Camille Garnier: Stress and Cancer Laboratory, Institut Curie
Sophie Abelanet: Stress and Cancer Laboratory, Institut Curie
Yann Kieffer: Stress and Cancer Laboratory, Institut Curie
Vincent Lemesre: Stress and Cancer Laboratory, Institut Curie
Dorine Bellanger: Inserm, Genetics and Biology of Cancers, U830
Ivan Bieche: Institut Curie
Elisabetta Marangoni: Laboratory of Precinical Investigation, Institut Curie
Xavier Sastre-Garau: Institut Curie
Virginie Mieulet: Stress and Cancer Laboratory, Institut Curie
Fatima Mechta-Grigoriou: Stress and Cancer Laboratory, Institut Curie

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract Ovarian cancer is a silent disease with a poor prognosis that urgently requires new therapeutic strategies. In low-grade ovarian tumours, mutations in the MAP3K BRAF gene constitutively activate the downstream kinase MEK. Here we demonstrate that an additional MAP3K, MAP3K8 (TPL-2/COT), accumulates in high-grade serous ovarian carcinomas (HGSCs) and is a potential prognostic marker for these tumours. By combining analyses on HGSC patient cohorts, ovarian cancer cells and patient-derived xenografts, we demonstrate that MAP3K8 controls cancer cell proliferation and migration by regulating key players in G1/S transition and adhesion dynamics. In addition, we show that the MEK pathway is the main pathway involved in mediating MAP3K8 function, and that MAP3K8 exhibits a reliable predictive value for the effectiveness of MEK inhibitor treatment. Our data highlight key roles for MAP3K8 in HGSC and indicate that MEK inhibitors could be a useful treatment strategy, in combination with conventional chemotherapy, for this disease.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms9583 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:6:y:2015:i:1:d:10.1038_ncomms9583

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

DOI: 10.1038/ncomms9583

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 ().