癌症相关 ENO2 通过介导组蛋白乳酸化诱导 M2 型巨噬细胞极化促进头颈部鳞状细胞癌的转移

Engineering ›› 2025, Vol. 48 ›› Issue (5) : 262 -276. DOI: 10.1016/j.eng.2024.11.036

研究论文

王晨然 ^a^,^b^,^c^,^d ,
谭霖 ^a^,^c^,^d ,
黄茂华 ^a^,^c^,^d ,
林宇宁 ^a^,^c^,^d ,
蔡明详 ^b ,
邓丽娟 ^a^,^c^,^e ,
胡欣朋 ^f ,
邱胜辉 ^g ,
陈晓婷 ^a^,^c^,^d ,
张益铭 ^a^,^c^,^d ,
罗小美 ^a^,^c^,^d ,
史长征 ^f ,
陈敏锋 ^a^,^c^,^d ,
叶文才 ^a^,^c^,^d ,
张君秋 ^a^,^c^,^d^,^* ,
张冬梅 ^a^,^c^,^d^,^* ,
刘湘宁 ^b^,^*

作者信息 +

Cancer ENO2 Induces Histone Lactylation-Mediated M2 Macrophage Polarization and Facilitates Metastasis of Head and Neck Squamous Cell Carcinoma

Chenran Wang ^a^,^b^,^c^,^d^,^# ,
Lin Tan ^a^,^c^,^d^,^# ,
Maohua Huang ^a^,^c^,^d^,^# ,
Yuning Lin ^a^,^c^,^d ,
Minxiang Cai ^b ,
Lijuan Deng ^a^,^c^,^e ,
Xinpeng Hu ^f ,
Shenghui Qiu ^g ,
Xiaoting Chen ^a^,^c^,^d ,
Yiming Zhang ^a^,^c^,^d ,
Xiaomei Luo ^a^,^c^,^d ,
Changzheng Shi ^f ,
Minfeng Chen ^a^,^c^,^d ,
Wencai Ye ^a^,^c^,^d ,
Junqiu Zhang ^a^,^c^,^d^,^* ,
Dongmei Zhang ^a^,^c^,^d^,^* ,
Xiangning Liu ^b^,^*

Author information +

^aState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Pharmacy, Jinan University, Guangzhou 510632, China

^bStomatological Hospital of The First Affiliated Hospital of Jinan University, Clinical Research Platform for Interdiscipline of Stomatology, School of Stomatology, Jinan University, Guangzhou 510630, China

^cGuangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou 510632, China

^dGuangdong–Hong Kong–Macau Joint Laboratory for Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou 510632, China

^eGuangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China

^fMedical Imaging Center, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510630, China

^gDepartment of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510630, China

* E-mail address: jqzhang@jnu.edu.cn

E-mail address: dmzhang701@jnu.edu.cn

E-mail address: liuxiangning@jnu.edu.cn

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文章历史 +

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Abstract

Metabolic reprogramming reshapes the tumor microenvironment (TME) and facilitates metastasis, but its molecular mechanisms remain incompletely understood. Here, we identified enolase 2 (ENO2), a critical glycolytic enzyme, as being associated with lymphatic metastasis in head and neck squamous cell carcinoma (HNSCC). Mechanistically, phosphoenolpyruvate (PEP), the metabolite secreted by ENO2-expressing HNSCC cells, drove histone H3 lysine 18 lactylation (H3K18la)-mediated M2 polarization in macrophages, which, in turn, enhanced the epithelial–mesenchymal transition (EMT) and invasiveness of HNSCC cells. Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis. Collectively, our findings underscore the prognostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC. Furthermore, we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.

关键词

烯醇化酶2（ENO2） / 头颈部鳞状细胞癌 / 肿瘤淋巴结转移 / 磷酸烯醇丙酮酸 / 组蛋白H3第18位赖氨酸乳酸化（H3K18la） / M2型巨噬细胞

Key words

ENO2 / HNSCC / Lymph node metastasis / Phosphoenolpyruvate / H3K18la / M2 macrophages

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王晨然,谭霖,黄茂华,林宇宁,蔡明详,邓丽娟,胡欣朋,邱胜辉,陈晓婷,张益铭,罗小美,史长征,陈敏锋,叶文才,张君秋,张冬梅,刘湘宁. 癌症相关 ENO2 通过介导组蛋白乳酸化诱导 M2 型巨噬细胞极化促进头颈部鳞状细胞癌的转移[J]. 工程（英文）, 2025, 48(5): 262-276 DOI:10.1016/j.eng.2024.11.036