An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer

Adrian Vallejo, Naiara Perurena, Elisabet Guruceaga, Pawel K. Mazur, Susana Martinez-Canarias, Carolina Zandueta, Karmele Valencia, Andrea Arricibita, Dana Gwinn, Leanne C. Sayles, Chen-Hua Chuang, Laura Guembe, Peter Bailey, David K. Chang, Andrew Biankin, Mariano Ponz-Sarvise, Jesper B. Andersen, Purvesh Khatri, Aline Bozec, E. Alejandro Sweet-Cordero, Julien Sage, Fernando Lecanda and Silve Vicent ()
Additional contact information
Adrian Vallejo: University of Navarra, Center for Applied Medical Research, Program in Solid Tumors and Biomarkers
Naiara Perurena: University of Navarra, Center for Applied Medical Research, Program in Solid Tumors and Biomarkers
Elisabet Guruceaga: University of Navarra, Center for Applied Medical Research, Proteomics, Genomics and Bioinformatics Core Facility
Pawel K. Mazur: Stanford University School of Medicine
Susana Martinez-Canarias: University of Navarra, Center for Applied Medical Research, Program in Solid Tumors and Biomarkers
Carolina Zandueta: University of Navarra, Center for Applied Medical Research, Program in Solid Tumors and Biomarkers
Karmele Valencia: University of Navarra, Center for Applied Medical Research, Program in Solid Tumors and Biomarkers
Andrea Arricibita: University of Navarra, Center for Applied Medical Research, Program in Solid Tumors and Biomarkers
Dana Gwinn: Stanford University School of Medicine
Leanne C. Sayles: Stanford University School of Medicine
Chen-Hua Chuang: Stanford University School of Medicine
Laura Guembe: University of Navarra, Center for Applied Medical Research, Morphology Unit
Peter Bailey: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate
David K. Chang: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate
Andrew Biankin: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate
Mariano Ponz-Sarvise: University of Navarra, Center for Applied Medical Research, Program in Solid Tumors and Biomarkers
Jesper B. Andersen: Biotech Research and Innovation Center, University of Copenhagen
Purvesh Khatri: Stanford Institute for Immunity, Transplantation and Infection
Aline Bozec: University of Erlangen-Nuremberg
E. Alejandro Sweet-Cordero: Stanford University School of Medicine
Julien Sage: Stanford University School of Medicine
Fernando Lecanda: University of Navarra, Center for Applied Medical Research, Program in Solid Tumors and Biomarkers
Silve Vicent: University of Navarra, Center for Applied Medical Research, Program in Solid Tumors and Biomarkers

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identifies mutant KRAS lung and pancreatic cancer patients with the worst survival outcome. Furthermore, FOSL1 genetic inhibition is detrimental to both KRAS-driven tumour types. Mechanistically, FOSL1 links the KRAS oncogene to components of the mitotic machinery, a pathway previously postulated to function orthogonally to oncogenic KRAS. FOSL1 targets include AURKA, whose inhibition impairs viability of mutant KRAS cells. Lastly, combination of AURKA and MEK inhibitors induces a deleterious effect on mutant KRAS cells. Our findings unveil KRAS downstream effectors that provide opportunities to treat KRAS-driven cancers.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/ncomms14294 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:8:y:2017:i:1:d:10.1038_ncomms14294

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

DOI: 10.1038/ncomms14294

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 ().