강유나 (경북대학교)

한빛사논문

조회205

강유나Yoo Na Kang

경북대학교

Exp. Mol. Med., May 01 2024, | https://doi.org/10.1038/s12276-024-01214-1 Glutamine-derived aspartate is required for eIF5A hypusination-mediated translation of HIF-1α to induce the polarization of tumor-associated macrophages

Dong-Ho Kim^1,9, Yoo Na Kang^2,9, Jonghwa Jin³, Mihyang Park³, Daehoon Kim¹, Ghilsuk Yoon⁴, Jae Won Yun⁵, Jaebon Lee⁵, Soo Young Park³, Yu Rim Lee⁶, Jun-Kyu Byun⁷, Yeon-Kyung Choi^6,8 and Keun-Gyu Park^1,3,8

¹Department of Biomedical Science, Kyungpook National University, Daegu 41566, South Korea.

²Department of Forensic Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, South Korea.

³Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, South Korea.

⁴Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Daegu 41404, South Korea.

⁵Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, South Korea.

⁶Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, South Korea.

⁷BK21 FOUR Community‑Based Intelligent Novel Drug Discovery Education Unit, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, South Korea.

⁸Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41566, South Korea.

⁹These authors contributed equally: Dong-Ho Kim, Yoo Na Kang.

Correspondence to Jun-Kyu Byun, Yeon-Kyung Choi or Keun-Gyu Park.

Abstract

Tumor-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.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-02)
연구진국내 연구진
분야 의약학 > 응용의학

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