Author:
Kim Dong-Ho,Kang Yoo Na,Jin Jonghwa,Park Mihyang,Kim Daehoon,Yoon Ghilsuk,Yun Jae Won,Lee Jaebon,Park Soo Young,Lee Yu Rim,Byun Jun-Kyu,Choi Yeon-Kyung,Park Keun-Gyu
Abstract
AbstractTumor-associated macrophages (TAMs) are vital contributors to the growth, metastasis, and therapeutic resistance of various cancers, including hepatocellular carcinoma (HCC). However, the exact phenotype of TAMs and the mechanisms underlying their modulation for therapeutic purposes have not been determined. Here, we present compelling evidence that glutamine-derived aspartate in TAMs stimulates spermidine production through the polyamine synthesis pathway, thereby increasing the translation efficiency of HIF-1α via eIF5A hypusination. Consequently, augmented translation of HIF-1α drives TAMs to undergo an increase glycolysis and acquire a metabolic phenotype distinct from that of M2 macrophages. Finally, eIF5A levels in tumor stromal lesions were greater than those in nontumor stromal lesions. Additionally, a higher degree of tumor stromal eIF5A hypusination was significantly associated with a more advanced tumor stage. Taken together, these data highlight the potential of inhibiting hypusinated eIF5A by targeting glutamine metabolism in TAMs, thereby opening a promising avenue for the development of novel therapeutic approaches for HCC.
Funder
National Research Foundation of Korea
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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