食管癌内缺氧微环境是促进恶性肿瘤快速进展的重要因素。本研究旨在探讨缺氧条件下Axin1的乳酰化对食管癌细胞糖酵解的影响。缺氧处理会增加 TE1 和 EC109 细胞的泛赖氨酸乳酰化 (pan-kla) 水平。同时，TE1 和 EC109 细胞中的 ECAR、葡萄糖消耗和乳酸生成也上调。缺氧处理的细胞中胚胎干细胞转录因子NANOG和SOX2的表达增强。 Axin1 过表达部分逆转了 TE1 和 EC109 细胞中缺氧处理的诱导作用。此外，缺氧处理诱导的Axin1蛋白K147处的乳酰化促进Axin1蛋白的泛素化修饰，从而促进TE1和EC109细胞的糖酵解和细胞干性。突变体Axin1可以在正常或缺氧条件下抑制TE1和EC109细胞的ECAR、葡萄糖摄取、乳酸分泌和细胞干性。同时，突变体Axin1进一步增强了2-DG抑制糖酵解和细胞干性的作用。 Axin1 的过度表达还抑制体内肿瘤生长，并且与抑制糖酵解有关。总之，缺氧处理促进了食管癌细胞的糖酵解和细胞干性，并增加了Axin1蛋白的乳酰化。 Axin1 的过度表达起到糖酵解抑制剂的作用，在体外抑制缺氧暴露的影响，在体内抑制肿瘤生长。从机械角度来看，缺氧会诱导 Axin1 蛋白乳酰化，并促进 Axin1 泛素化，从而降解该蛋白，从而发挥其抗糖酵解功能。版权所有 © 2024。由 Elsevier Inc. 出版。

The hypoxic microenvironment in esophageal carcinoma is an important factor promoting the rapid progression of malignant tumor. This study was to investigate the lactylation of Axin1 on glycolysis in esophageal carcinoma cells under hypoxia exposure. Hypoxia treatment increases pan lysine lactylation (pan-kla) levels of both TE1 and EC109 cells. Meanwhile, ECAR, glucose consumption and lactate production were also upregulated in both TE1 and EC109 cells. The expression of embryonic stem cell transcription factors NANOG and SOX2 were enhanced in the hypoxia-treated cells. Axin1 overexpression partly reverses the induction effects of hypoxia treatment in TE1 and EC109 cells. Moreover, lactylation of Axin1 protein at K147 induced by hypoxia treatment promotes ubiquitination modification of Axin1 protein to promote glycolysis and cell stemness of TE1 and EC109 cells. Mutant Axin1 can inhibit ECAR, glucose uptake, lactate secretion, and cell stemness in TE1 and EC109 cells under normal or hypoxia conditions. Meanwhile, mutant Axin1 further enhanced the effects of 2-DG on inhibiting glycolysis and cell stemness. Overexpression of Axin1 also inhibited tumor growth in vivo, and was related to suppressing glycolysis. In conclusion, hypoxia treatment promoted the glycolysis and cell stemness of esophageal carcinoma cells, and increased the lactylation of Axin1 protein. Overexpression of Axin1 functioned as a glycolysis inhibitor, and suppressed the effects of hypoxia exposure in vitro and inhibited tumor growth in vivo. Mechanically, hypoxia induces the lactylation of Axin1 protein and promotes the ubiquitination of Axin1 to degrade the protein, thereby exercising its anti-glycolytic function.Copyright © 2024. Published by Elsevier Inc.