越来越多的证据表明 CD24 在肿瘤进展中的重要性，但其在食管鳞状细胞癌 (ESCC) 中的作用和机制仍不清楚。本研究旨在探讨 CD24 作为 ESCC 新型预测生物标志物的潜力，及其在转移和 5-FU 化疗耐药中的机制和治疗意义。通过使用组织微阵列和免疫组织化学，我们发现食管鳞癌肿瘤组织中CD24的表达高于配对的非肿瘤组织，进一步表明CD24与不良预后显着相关。 CD24在体外和体内显着促进转移和5-FU化疗耐药。从机制上讲，CD24与GIT2竞争结合Arf6，并稳定Arf6-GTP以激活后续的ERK通路，从而促进癌症进展。此外，在临床ESCC组织中观察到CD24和p-ERK之间存在显着的正相关性。总之，本研究不仅揭示了 CD24 作为 Arf6 活性的调节因子，而且还揭示了 CD24-Arf6-ERK 信号轴作为 ESCC 进展的新机制。我们的研究结果表明 CD24 是 ESCC 中一种有前途的生物标志物和治疗靶点。版权所有 © 2024。由 Elsevier B.V. 出版。

Increasing evidence suggests the importance of CD24 in tumor progression, but its role and mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. The present study aims to explore the potential of CD24 as a novel predictive biomarker in ESCC, as well as its mechanism and therapeutic implications in metastasis and 5-FU chemoresistance. By using tissue microarray and immunohistochemistry, we found that CD24 expression was higher in ESCC tumor tissues than paired non-tumor tissues, further indicating that CD24 was markedly associated with poor prognosis. CD24 significantly promoted metastasis and 5-FU chemoresistance in vitro and in vivo. Mechanistically, CD24 competes with GIT2 to bind to Arf6, and stabilizes Arf6-GTP to activate the subsequent ERK pathway, thus promoting cancer progression. In addition, a significant positive correlation between CD24 and p-ERK was observed in clinical ESCC tissues. In summary, this study not only reveals CD24 as a regulatory factor for Arf6 activity, but also uncovers CD24-Arf6-ERK signaling axis as a novel mechanism of ESCC progression. Our findings suggest CD24 as a promising biomarker and therapeutic target in ESCC.Copyright © 2024. Published by Elsevier B.V.