Cargando…

EIF4A3 Acts on the PI3K–AKT–ERK1/2–P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) is a major lung cancer subtype. In this study, we discovered that the eukaryotic translation initiation factor EIF4A3 expression was significantly higher in LUAD tissues and that this higher expression was closely linked to a poor prognosis for LUAD. In addition, we demons...

Descripción completa

Detalles Bibliográficos
Autores principales: Yu, Wenhao, Liang, Jinghui, Fang, Tao, Jiang, Jin, Zhao, Renchang, Li, Rongyang, Han, Jingyi, Tian, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320473/
https://www.ncbi.nlm.nih.gov/pubmed/37011005
http://dx.doi.org/10.1158/1541-7786.MCR-22-0984
_version_ 1785068456308113408
author Yu, Wenhao
Liang, Jinghui
Fang, Tao
Jiang, Jin
Zhao, Renchang
Li, Rongyang
Han, Jingyi
Tian, Hui
author_facet Yu, Wenhao
Liang, Jinghui
Fang, Tao
Jiang, Jin
Zhao, Renchang
Li, Rongyang
Han, Jingyi
Tian, Hui
author_sort Yu, Wenhao
collection PubMed
description Lung adenocarcinoma (LUAD) is a major lung cancer subtype. In this study, we discovered that the eukaryotic translation initiation factor EIF4A3 expression was significantly higher in LUAD tissues and that this higher expression was closely linked to a poor prognosis for LUAD. In addition, we demonstrated that the knockdown of EIF4A3 significantly inhibited the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. The findings of mass spectrometry analysis revealed that EIF4A3 could interact with Flotillin-1 in LUAD cells and that EIF4A3 could positively regulate the expression of FLOT1 at the protein level. Meanwhile, transcriptome sequencing showed that EIF4A3 could influence the development of LUAD by affecting PI3K–AKT–ERK1/2–P70S6K and PI3K class III–mediated autophagy in the Apelin pathway. In addition, we confirmed that Flotillin-1 expression was upregulated in LUAD based on the existing literature, and knockdown of FLOT1 could inhibit the proliferation and migration of LUAD cells. In addition, the knockdown of Flotillin-1 reversed the increase of cell proliferation and migration caused by EIF4A3 overexpression. Furthermore, we found that the activation of PI3K–AKT–ERK1/2–P70S6K signaling pathway and PI3K class III–mediated autophagy caused by EIF4A3 overexpression was rescued by the knockdown of FLOT1. In a word, we proved that EIF4A3 positively regulates the expression of FLOT1 and plays a procancer role in LUAD. IMPLICATIONS: Our study revealed the role of EIF4A3 in prognosis and tumor progression in LUAD, indicating that EIF4A3 could be used as the molecular diagnostic and prognostic therapeutic target.
format Online
Article
Text
id pubmed-10320473
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Association for Cancer Research
record_format MEDLINE/PubMed
spelling pubmed-103204732023-07-06 EIF4A3 Acts on the PI3K–AKT–ERK1/2–P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma Yu, Wenhao Liang, Jinghui Fang, Tao Jiang, Jin Zhao, Renchang Li, Rongyang Han, Jingyi Tian, Hui Mol Cancer Res Signal Transduction and Functional Imaging Lung adenocarcinoma (LUAD) is a major lung cancer subtype. In this study, we discovered that the eukaryotic translation initiation factor EIF4A3 expression was significantly higher in LUAD tissues and that this higher expression was closely linked to a poor prognosis for LUAD. In addition, we demonstrated that the knockdown of EIF4A3 significantly inhibited the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. The findings of mass spectrometry analysis revealed that EIF4A3 could interact with Flotillin-1 in LUAD cells and that EIF4A3 could positively regulate the expression of FLOT1 at the protein level. Meanwhile, transcriptome sequencing showed that EIF4A3 could influence the development of LUAD by affecting PI3K–AKT–ERK1/2–P70S6K and PI3K class III–mediated autophagy in the Apelin pathway. In addition, we confirmed that Flotillin-1 expression was upregulated in LUAD based on the existing literature, and knockdown of FLOT1 could inhibit the proliferation and migration of LUAD cells. In addition, the knockdown of Flotillin-1 reversed the increase of cell proliferation and migration caused by EIF4A3 overexpression. Furthermore, we found that the activation of PI3K–AKT–ERK1/2–P70S6K signaling pathway and PI3K class III–mediated autophagy caused by EIF4A3 overexpression was rescued by the knockdown of FLOT1. In a word, we proved that EIF4A3 positively regulates the expression of FLOT1 and plays a procancer role in LUAD. IMPLICATIONS: Our study revealed the role of EIF4A3 in prognosis and tumor progression in LUAD, indicating that EIF4A3 could be used as the molecular diagnostic and prognostic therapeutic target. American Association for Cancer Research 2023-07-05 2023-04-03 /pmc/articles/PMC10320473/ /pubmed/37011005 http://dx.doi.org/10.1158/1541-7786.MCR-22-0984 Text en ©2023 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
spellingShingle Signal Transduction and Functional Imaging
Yu, Wenhao
Liang, Jinghui
Fang, Tao
Jiang, Jin
Zhao, Renchang
Li, Rongyang
Han, Jingyi
Tian, Hui
EIF4A3 Acts on the PI3K–AKT–ERK1/2–P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma
title EIF4A3 Acts on the PI3K–AKT–ERK1/2–P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma
title_full EIF4A3 Acts on the PI3K–AKT–ERK1/2–P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma
title_fullStr EIF4A3 Acts on the PI3K–AKT–ERK1/2–P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma
title_full_unstemmed EIF4A3 Acts on the PI3K–AKT–ERK1/2–P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma
title_short EIF4A3 Acts on the PI3K–AKT–ERK1/2–P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma
title_sort eif4a3 acts on the pi3k–akt–erk1/2–p70s6k pathway through flot1 to influence the development of lung adenocarcinoma
topic Signal Transduction and Functional Imaging
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320473/
https://www.ncbi.nlm.nih.gov/pubmed/37011005
http://dx.doi.org/10.1158/1541-7786.MCR-22-0984
work_keys_str_mv AT yuwenhao eif4a3actsonthepi3kakterk12p70s6kpathwaythroughflot1toinfluencethedevelopmentoflungadenocarcinoma
AT liangjinghui eif4a3actsonthepi3kakterk12p70s6kpathwaythroughflot1toinfluencethedevelopmentoflungadenocarcinoma
AT fangtao eif4a3actsonthepi3kakterk12p70s6kpathwaythroughflot1toinfluencethedevelopmentoflungadenocarcinoma
AT jiangjin eif4a3actsonthepi3kakterk12p70s6kpathwaythroughflot1toinfluencethedevelopmentoflungadenocarcinoma
AT zhaorenchang eif4a3actsonthepi3kakterk12p70s6kpathwaythroughflot1toinfluencethedevelopmentoflungadenocarcinoma
AT lirongyang eif4a3actsonthepi3kakterk12p70s6kpathwaythroughflot1toinfluencethedevelopmentoflungadenocarcinoma
AT hanjingyi eif4a3actsonthepi3kakterk12p70s6kpathwaythroughflot1toinfluencethedevelopmentoflungadenocarcinoma
AT tianhui eif4a3actsonthepi3kakterk12p70s6kpathwaythroughflot1toinfluencethedevelopmentoflungadenocarcinoma