Spatial patterns of the cap-binding complex eIF4F in human melanoma cells

As a central node of protein synthesis, the cap-binding complex, eukaryotic translation initiation factor 4 F (eIF4F), is involved in cell homeostasis, development and tumorigenesis. A large body of literature exists on the regulation and function of eIF4F in cancer cells, however the intracellular...

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Main Authors: Xinpu Tang, Yi Pu, Haoning Peng, Kaixiu Li, Sara Faouzi, Tianjian Lu, Dan Pu, Michael Cerezo, Jianguo Xu, Lu Li, Caroline Robert, Shensi Shen
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Computational and Structural Biotechnology Journal
Online Access:http://www.sciencedirect.com/science/article/pii/S2001037023000429
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author Xinpu Tang
Yi Pu
Haoning Peng
Kaixiu Li
Sara Faouzi
Tianjian Lu
Dan Pu
Michael Cerezo
Jianguo Xu
Lu Li
Caroline Robert
Shensi Shen
author_facet Xinpu Tang
Yi Pu
Haoning Peng
Kaixiu Li
Sara Faouzi
Tianjian Lu
Dan Pu
Michael Cerezo
Jianguo Xu
Lu Li
Caroline Robert
Shensi Shen
author_sort Xinpu Tang
collection DOAJ
description As a central node of protein synthesis, the cap-binding complex, eukaryotic translation initiation factor 4 F (eIF4F), is involved in cell homeostasis, development and tumorigenesis. A large body of literature exists on the regulation and function of eIF4F in cancer cells, however the intracellular localization patterns of this complex are largely unknown. Since different subsets of mRNAs are translated in distinct subcellular compartments, understanding the distribution of translation initiation factors in the cell is of major interest. Here, we developed an in situ detection method for eIF4F at the single cell level. By using an image-based spot feature analysis pipeline as well as supervised machine learning, we identify five distinct spatial patterns of the eIF4F translation initiation complex in human melanoma cells. The quantity of eIF4F complex per cell correlated with the global mRNA translation activity, and its variation is dynamically regulated by cell state or extracellular stimuli. In contrast, the spatial patterns of eIF4F complexes at the single cell level could distinguish melanoma cells harboring different oncogenic driver mutations. This suggests that different tumorigenic contexts differentially regulate the subcellular localization of mRNA translation, with specific localization of eIF4F potentially associated with melanoma cell chemoresistance.
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spelling doaj.art-2ce22105fa7342faa45c4c03c11f181c2023-12-21T07:30:53ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012111571168Spatial patterns of the cap-binding complex eIF4F in human melanoma cellsXinpu Tang0Yi Pu1Haoning Peng2Kaixiu Li3Sara Faouzi4Tianjian Lu5Dan Pu6Michael Cerezo7Jianguo Xu8Lu Li9Caroline Robert10Shensi Shen11Institute of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, China; Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, ChinaInstitute of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, China; Department of Burn Surgery, West China Hospital of Sichuan University, Chengdu, ChinaInstitute of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, China; Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, ChinaInstitute of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, ChinaINSERM U981, Gustave Roussy Cancer Campus, Villejuif, FranceInstitute of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, China; Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, ChinaLung Cancer Center, West China Hospital of Sichuan University, Chengdu, ChinaUniversité Côte d′Azur, Nice, France; Centre Méditerranéen de Médicine Moléculaire (C3M), INSERM U1065, Equipe 12, Nice, FranceDepartment of Neurosurgery, West China Hospital of Sichuan University, Chengdu, ChinaLung Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Corresponding author.INSERM U981, Gustave Roussy Cancer Campus, Villejuif, France; Dermatology Unit, Gustave Roussy Cancer Campus, Villejuif, France; Corresponding author at: INSERM U981, Gustave Roussy Cancer Campus, Villejuif, France.Institute of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, China; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China; Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, China; Correspondence to: Institute of Thoracic Oncology and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.As a central node of protein synthesis, the cap-binding complex, eukaryotic translation initiation factor 4 F (eIF4F), is involved in cell homeostasis, development and tumorigenesis. A large body of literature exists on the regulation and function of eIF4F in cancer cells, however the intracellular localization patterns of this complex are largely unknown. Since different subsets of mRNAs are translated in distinct subcellular compartments, understanding the distribution of translation initiation factors in the cell is of major interest. Here, we developed an in situ detection method for eIF4F at the single cell level. By using an image-based spot feature analysis pipeline as well as supervised machine learning, we identify five distinct spatial patterns of the eIF4F translation initiation complex in human melanoma cells. The quantity of eIF4F complex per cell correlated with the global mRNA translation activity, and its variation is dynamically regulated by cell state or extracellular stimuli. In contrast, the spatial patterns of eIF4F complexes at the single cell level could distinguish melanoma cells harboring different oncogenic driver mutations. This suggests that different tumorigenic contexts differentially regulate the subcellular localization of mRNA translation, with specific localization of eIF4F potentially associated with melanoma cell chemoresistance.http://www.sciencedirect.com/science/article/pii/S2001037023000429
spellingShingle Xinpu Tang
Yi Pu
Haoning Peng
Kaixiu Li
Sara Faouzi
Tianjian Lu
Dan Pu
Michael Cerezo
Jianguo Xu
Lu Li
Caroline Robert
Shensi Shen
Spatial patterns of the cap-binding complex eIF4F in human melanoma cells
Computational and Structural Biotechnology Journal
title Spatial patterns of the cap-binding complex eIF4F in human melanoma cells
title_full Spatial patterns of the cap-binding complex eIF4F in human melanoma cells
title_fullStr Spatial patterns of the cap-binding complex eIF4F in human melanoma cells
title_full_unstemmed Spatial patterns of the cap-binding complex eIF4F in human melanoma cells
title_short Spatial patterns of the cap-binding complex eIF4F in human melanoma cells
title_sort spatial patterns of the cap binding complex eif4f in human melanoma cells
url http://www.sciencedirect.com/science/article/pii/S2001037023000429
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