ArticleJournal of translational medicine2019
Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α.
Article in Journal of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
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- The integrated stress response is activated in the salivary glands of Sjögren's syndrome patients.Frontiers in medicine · 2023Article
- Tomatine Displays Antitumor Potential in In Vitro Models of Metastatic Melanoma.International journal of molecular sciences · 2020Article
- A New Look at the Structures of Old Sepsis Actors by Exploratory Data Analysis Tools.Antibiotics (Basel, Switzerland) · 2019Article
- MITF controls the TCA cycle to modulate the melanoma hypoxia response.Pigment cell & melanoma research · 2019Article
- The Complex Role of Autophagy in Melanoma Evolution: New Perspectives From Mouse Models.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMelanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported.
methodsWe evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma.
resultsWe found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells.
conclusionsBased on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma.
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