Targeted inhibition of eIF5Ahpu suppresses tumor growth and polarization of M2-like tumor-associated macrophages in oral cancer
Abstract Eukaryotic initiation factor 5A2 (eIF5A2) is overexpressed in many types of cancer, and spermidine-mediated eIF5A hypusination (eIF5A hpu ) appears to be essential to most of eIF5A’s biological functions, including its important role in regulating cancer cell proliferation, epithelial–mesen...
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Published in | Cell death & disease Vol. 14; no. 8; p. 579 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Springer Nature B.V
31.08.2023
Nature Publishing Group UK Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Abstract
Eukaryotic initiation factor 5A2 (eIF5A2) is overexpressed in many types of cancer, and spermidine-mediated eIF5A hypusination (eIF5A
hpu
) 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
hpu
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
hpu
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
hpu
robustly inhibited OSCC-induced M2-like TAM polarization in vitro. More Importantly, blocking eIF5A
hpu
dramatically retarded tumor growth and infiltration/polarization of M2-like TAM in a syngeneic orthotopic murine tongue SCC model. Thus, eIF5A
hpu
plays dual functions in regulating tumor cell growth and polarization of M2-TAMs in OSCC. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-4889 2041-4889 |
DOI: | 10.1038/s41419-023-06109-z |