Nuclear control of lung cancer cells migration, invasion and bioenergetics by eukaryotic translation initiation factor 3F
| Autor: | Rodrigue Rossignol, Saharnaz Sarlak, Nivea Dias Amoedo, Jean-William Dupuy, Pauline Esteves, Marc Bonneu, Didier Lacombe, Laetitia Dard, Christophe Hubert, Elodie Dumon, Aurélia Brillac, Benoit Rousseau, Julien Izotte |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Cancer Research Lung Neoplasms Nitrofurans Eukaryotic Initiation Factor-3 Cell Datasets as Topic Proteomics Biochemistry Oxidative Phosphorylation Mice 0302 clinical medicine Cell Movement Hydroxybenzoates RNA-Seq RNA Small Interfering STAT3 Lung Cancer Cell migration Cell biology Gene Expression Regulation Neoplastic medicine.anatomical_structure Gene Knockdown Techniques 030220 oncology & carcinogenesis STAT3 Transcription Factor Adenocarcinoma of Lung Biology Article 03 medical and health sciences Eukaryotic translation Genetics medicine Animals Humans Initiation factor Neoplasm Invasiveness Protein kinase A Molecular Biology Cell Nucleus Survival Analysis Xenograft Model Antitumor Assays 030104 developmental biology A549 Cells Mutation biology.protein Snail Family Transcription Factors Energy Metabolism Nuclear localization sequence HeLa Cells |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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