Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis

Abstract eIF4G1, a critical component of the eIF4F complex, is required for cap-dependent mRNA translation, a process necessary for tumor growth and survival. However, the role of eIF4G1 has not been evaluated in Prostate Cancer (PCa). We observed an increased eIF4G1 protein levels in PCa tissues as...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Praveen Kumar Jaiswal, Sweaty Koul, Prakash S. T. Shanmugam, Hari K. Koul
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a495c3363f0747548755798c999d741f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a495c3363f0747548755798c999d741f
record_format	dspace
spelling	oai:doaj.org-article:a495c3363f0747548755798c999d741f2021-12-02T15:07:48ZEukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis10.1038/s41598-018-25798-72045-2322https://doaj.org/article/a495c3363f0747548755798c999d741f2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25798-7https://doaj.org/toc/2045-2322Abstract eIF4G1, a critical component of the eIF4F complex, is required for cap-dependent mRNA translation, a process necessary for tumor growth and survival. However, the role of eIF4G1 has not been evaluated in Prostate Cancer (PCa). We observed an increased eIF4G1 protein levels in PCa tissues as compared to normal tissues. Analysis of the TCGA data revealed that eIF4G1 gene expression positively correlated with higher tumor grade and stage. Furthermore, eIF4G1 was over-expressed and or amplified, in 16% patients with metastatic PCa (SU2C/PCF Dream Team dataset) and in 59% of castration-resistant prostate cancer (CRPC) patients (Trento/Cornell/Broad dataset). We showed for the first time that eIF4G1 expression was increased in PCa and that increased eIF4G1 expression associated with tumor progression and metastasis. We also observed high protein levels of eIF4G1 in PCa cell lines and prostate tissues from the TRAMP model of PCa as compared to normal prostate cell line and prostate tissues from the wild type mice. Knockdown of eIF4G1 in PCa cells resulted in decreased Cyclin D1 and p-Rb protein level, cell cycle delay, reduced cell viability and proliferation, impaired clonogenic activity, reduced cell migration and decreased mRNA loading to polysomes. Treatment with eIF4G complex inhibitor also impaired prostasphere formation. eIF4G1 knockdown or treatment with eIF4G complex inhibitor sensitized CRPC cells to Enzalutamide and Bicalutamide. Our results showed that eIF4G1 plays an important role in PCa growth and therapeutic resistance. These data suggested that eIF4G1 functions as an oncoprotein and may serve as a novel target for intervention in PCa and CRPC.Praveen Kumar JaiswalSweaty KoulPrakash S. T. ShanmugamHari K. KoulNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Praveen Kumar Jaiswal Sweaty Koul Prakash S. T. Shanmugam Hari K. Koul Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis
description	Abstract eIF4G1, a critical component of the eIF4F complex, is required for cap-dependent mRNA translation, a process necessary for tumor growth and survival. However, the role of eIF4G1 has not been evaluated in Prostate Cancer (PCa). We observed an increased eIF4G1 protein levels in PCa tissues as compared to normal tissues. Analysis of the TCGA data revealed that eIF4G1 gene expression positively correlated with higher tumor grade and stage. Furthermore, eIF4G1 was over-expressed and or amplified, in 16% patients with metastatic PCa (SU2C/PCF Dream Team dataset) and in 59% of castration-resistant prostate cancer (CRPC) patients (Trento/Cornell/Broad dataset). We showed for the first time that eIF4G1 expression was increased in PCa and that increased eIF4G1 expression associated with tumor progression and metastasis. We also observed high protein levels of eIF4G1 in PCa cell lines and prostate tissues from the TRAMP model of PCa as compared to normal prostate cell line and prostate tissues from the wild type mice. Knockdown of eIF4G1 in PCa cells resulted in decreased Cyclin D1 and p-Rb protein level, cell cycle delay, reduced cell viability and proliferation, impaired clonogenic activity, reduced cell migration and decreased mRNA loading to polysomes. Treatment with eIF4G complex inhibitor also impaired prostasphere formation. eIF4G1 knockdown or treatment with eIF4G complex inhibitor sensitized CRPC cells to Enzalutamide and Bicalutamide. Our results showed that eIF4G1 plays an important role in PCa growth and therapeutic resistance. These data suggested that eIF4G1 functions as an oncoprotein and may serve as a novel target for intervention in PCa and CRPC.
format	article
author	Praveen Kumar Jaiswal Sweaty Koul Prakash S. T. Shanmugam Hari K. Koul
author_facet	Praveen Kumar Jaiswal Sweaty Koul Prakash S. T. Shanmugam Hari K. Koul
author_sort	Praveen Kumar Jaiswal
title	Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis
title_short	Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis
title_full	Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis
title_fullStr	Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis
title_full_unstemmed	Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis
title_sort	eukaryotic translation initiation factor 4 gamma 1 (eif4g1) is upregulated during prostate cancer progression and modulates cell growth and metastasis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/a495c3363f0747548755798c999d741f
work_keys_str_mv	AT praveenkumarjaiswal eukaryotictranslationinitiationfactor4gamma1eif4g1isupregulatedduringprostatecancerprogressionandmodulatescellgrowthandmetastasis AT sweatykoul eukaryotictranslationinitiationfactor4gamma1eif4g1isupregulatedduringprostatecancerprogressionandmodulatescellgrowthandmetastasis AT prakashstshanmugam eukaryotictranslationinitiationfactor4gamma1eif4g1isupregulatedduringprostatecancerprogressionandmodulatescellgrowthandmetastasis AT harikkoul eukaryotictranslationinitiationfactor4gamma1eif4g1isupregulatedduringprostatecancerprogressionandmodulatescellgrowthandmetastasis
_version_	1718388408620941312

Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis

Ejemplares similares