Targeted inhibition of eIF5A hpu suppresses tumor growth and polarization of M2-like tumor-associated macrophages in oral cancer

Eukaryotic initiation factor 5A2 (eIF5A2) is overexpressed in many types of cancer, and spermidine-mediated eIF5A hypusination (eIF5A ) appears to be essential to most of eIF5A's biological functions, including its important role in regulating cancer cell proliferation, epithelial-mesenchymal t...

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Published in:Cell death & disease 2023-08, Vol.14 (8), p.579
Main Authors: Zeng, Jincheng, Ye, Ziyu, Shi, Shihong, Liang, Yanfang, Meng, Qingyu, Zhang, Qunzhou, Le, Anh D
Format: Article
Language:English
Subjects:
Animals
Carcinoma, Squamous Cell
Eukaryotic Translation Initiation Factor 5A
Humans
Mice
Mouth Neoplasms - genetics
Peptide Initiation Factors - genetics
Tongue Neoplasms - genetics
Tumor-Associated Macrophages
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container_issue 8
container_start_page 579
container_title Cell death & disease
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creator Zeng, Jincheng
Ye, Ziyu
Shi, Shihong
Liang, Yanfang
Meng, Qingyu
Zhang, Qunzhou
Le, Anh D
description Eukaryotic initiation factor 5A2 (eIF5A2) is overexpressed in many types of cancer, and spermidine-mediated eIF5A hypusination (eIF5A ) appears to be essential to most of eIF5A's biological functions, including its important role in regulating cancer cell proliferation, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties as well as immune cell functions. Here we investigated the role of eIF5A in the growth of oral squamous cell carcinoma cells (OSCCs) and OSCC-induced polarization of M2-like tumor-associated macrophages (TAMs). TCGA dataset analysis revealed an overall upregulation in the mRNA expression of eIF5A2 and several key enzymes involved in polyamine (PA) metabolism in HNSCC, which was confirmed by Western blot and IHC studies. Blocking eIF5A by GC-7 but not the upstream key enzyme activities of PA metabolism, remarkably inhibited cell proliferation and the expression of EMT- and CSC-related genes in OSCC cells. In addition, blocking eIF5A robustly inhibited OSCC-induced M2-like TAM polarization in vitro. More Importantly, blocking eIF5A dramatically retarded tumor growth and infiltration/polarization of M2-like TAM in a syngeneic orthotopic murine tongue SCC model. Thus, eIF5A plays dual functions in regulating tumor cell growth and polarization of M2-TAMs in OSCC.
doi_str_mv 10.1038/s41419-023-06109-z
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source NCBI_PubMed Central（免费）; Publicly Available Content Database; Springer Nature - nature.com Journals - Fully Open Access
subjects Animals
Carcinoma, Squamous Cell
Eukaryotic Translation Initiation Factor 5A
Humans
Mice
Mouth Neoplasms - genetics
Peptide Initiation Factors - genetics
Tongue Neoplasms - genetics
Tumor-Associated Macrophages
title Targeted inhibition of eIF5A hpu suppresses tumor growth and polarization of M2-like tumor-associated macrophages in oral cancer
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