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Esteves 2019 Oncogene

From Bioblast
Publications in the MiPMap
Esteves P, Dard L, Brillac A, Hubert C, Sarlak S, Rousseau B, Dumon E, Izotte J, Bonneu M, Lacombe D, Dupuy JW, Amoedo N, Rossignol R (2019) Nuclear control of lung cancer cells migration, invasion and bioenergetics by eukaryotic translation initiation factor 3F. Oncogene 39:617-36.

Β» PMID: 31527668 Open Access

Esteves P, Dard L, Brillac A, Hubert C, Sarlak S, Rousseau B, Dumon E, Izotte J, Bonneu M, Lacombe D, Dupuy JW, Amoedo N, Rossignol R (2019) Oncogene

Abstract: The basic understanding of the biological effects of eukaryotic translation initiation factors (EIFs) remains incomplete, notably for their roles independent of protein translation. Different EIFs exhibit nuclear localization and DNA-related functions have been proposed, but the understanding of EIFs novel functions beyond protein translation lacks of integrative analyses between the genomic and the proteomic levels. Here, the noncanonical function of EIF3F was studied in human lung adenocarcinoma by combining methods that revealed both the protein-protein and the protein-DNA interactions of this factor. We discovered that EIF3F promotes cell metastasis in vivo. The underpinning molecular mechanisms involved the regulation of a cluster of 34 metastasis-promoting genes including Snail2, as revealed by proteomics combined with immuno-affinity purification of EIF3F and ChIP-seq/Q-PCR analyses. The interaction between EIF3F and signal transducer and activator of transcription 3 (STAT3) controlled the EIF3F-mediated increase in Snail2 expression and cellular invasion, which were specifically abrogated using the STAT3 inhibitor Nifuroxazide or knockdown approaches. Furthermore, EIF3F overexpression reprogrammed energy metabolism through the activation of AMP-activated protein kinase and the stimulation of oxidative phosphorylation. Our findings demonstrate the role of EIF3F in the molecular control of cell migration, invasion, bioenergetics, and metastasis. The discovery of a role for EIF3F-STAT3 interaction in the genetic control of cell migration and metastasis in human lung adenocarcinoma could lead to the development of diagnosis and therapeutic strategies.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: FR Bordeaux Rossignol R

Labels: MiParea: Respiration, nDNA;cell genetics, Genetic knockout;overexpression  Pathology: Cancer 

Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Permeabilized cells, Intact cells 

Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, ROX  HRR: Oxygraph-2k 

Labels, 2019-09