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Martinez-Férriz, AAuthorFerrando, AAuthor

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October 28, 2024
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Eukaryotic Initiation Factor 5A2 localizes to actively translating ribosomes to promote cancer cell protrusions and invasive capacity

Publicated to:Cell Communication And Signaling. 21 (1): 54- - 2023-03-13 21(1), DOI: 10.1186/s12964-023-01076-6

Authors: Martinez-Ferriz, Arantxa; Gandia, Carolina; Pardo-Sanchez, Jose Miguel; Fathinajafabadi, Alihamze; Ferrando, Alejandro; Farras, Rosa

Affiliations

Ctr Invest Principe Felipe - Author
Univ Politecn Valencia, Consejo Super Invest Cient, Inst Biol Mol & Celular Plantas - Author

Abstract

Background Eukaryotic Initiation Factor 5A (eIF-5A), an essential translation factor, is post-translationally activated by the polyamine spermidine. Two human genes encode eIF-5A, being eIF5-A1 constitutively expressed whereas eIF5-A2 is frequently found overexpressed in human tumours. The contribution of both isoforms with regard to cellular proliferation and invasion in non-small cell lung cancer remains to be characterized. Methods We have evaluated the use of eIF-5A2 gene as prognosis marker in lung adenocarcinoma (LUAD) patients and validated in immunocompromised mice. We have used cell migration and cell proliferation assays in LUAD lines after silencing each eIF-5A isoform to monitor their contribution to both phenotypes. Cytoskeleton alterations were analysed in the same cells by rhodamine-phalloidin staining and fluorescence microscopy. Polysome profiles were used to monitor the effect of eIF-5A2 overexpression on translation. Western blotting was used to study the levels of eIF-5A2 client proteins involved in migration upon TGFB1 stimulation. Finally, we have co-localized eIF-5A2 with puromycin to visualize the subcellular pattern of actively translating ribosomes. Results We describe the differential functions of both eIF-5A isoforms, to show that eIF5-A2 properties on cell proliferation and migration are coincident with its features as a poor prognosis marker. Silencing of eIF-5A2 leads to more dramatic consequences of cellular proliferation and migration compared to eIF-5A1. Overexpression of eIF5A2 leads to enhanced global translation. We also show that TGF ss signalling enhances the expression and activity of eIF-5A2 which promotes the translation of polyproline rich proteins involved in cytoskeleton and motility features as it is the case of Fibronectin, SNAI1, Ezrin and FHOD1. With the use of puromycin labelling we have co-localized active ribosomes with eIF-5A2 not only in cytosol but also in areas of cellular protrusion. We have shown the bulk invasive capacity of cells overexpressing eIF-5A2 in mice. Conclusions We propose the existence of a coordinated temporal and positional interaction between TFGB and eIF-5A2 pathways to promote cell migration in NSCLC. We suggest that the co-localization of actively translating ribosomes with hypusinated eIF-5A2 facilitates the translation of key proteins not only in the cytosol but also in areas of cellular protrusion.

Keywords

A-549 cell lineAggressivenessAmino acid sequenceAnimalAnimal experimentAnimal modelAnimal tissueAnimalsArticleBioinformaticsCancer cellCancer patientCarcinoma, non-small-cell lungCell invasionCell migrationCell migration assayCell proliferationCell proliferation assayConfocal microscopyControlled studyCytoskeleton organizationEpithelial mesenchymal transitionEukaryotic translation initiation factor 5a2ExpressionFactor eif5aFibronectinFlow cytometryFluorescence in situ hybridizationGene expressionGene overexpressionGeneticsHumanHuman cellHuman tissueHumansHypusineIdentificationImmunoblottingImmunofluorescence assayImmunohistochemistryInhibitionInitiation factorInitiation factor 5aLung adenocarcinomaLung neoplasmsLung tumorMetabolismMetastasisMiceMouseNon small cell lung cancerNonhumanOverexpressionPeptide initiation factorsPhalloidinPhenotypePolyaminePolysomeProteinProtein functionPuromycinRac1 proteinReal time polymerase chain reactionRibosomeRibosomesRna interferenceSignal transductionSmall interfering rnaTgf beta signalingTgf-betaTgfb1 signalingTransforming growth factor beta1Translating ribosomesTumor cellTumor volumeUpregulationWestern blotting

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cell Communication And Signaling due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 32/205, thus managing to position itself as a Q1 (Primer Cuartil), in the category Cell Biology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.32, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-09, the following number of citations:

  • WoS: 7
  • Scopus: 3
  • Europe PMC: 5

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-08-09:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 9.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 9 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 9.6.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 14 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (MARTÍNEZ FÉRRIZ, ARANTXA) .