2. Academic Validation
  3. CD24 promotes metastasis and chemoresistance by directly targeting Arf6-ERK pathway in esophageal squamous cell carcinoma

CD24 promotes metastasis and chemoresistance by directly targeting Arf6-ERK pathway in esophageal squamous cell carcinoma

  • Cancer Lett. 2024 May 25:594:216994. doi: 10.1016/j.canlet.2024.216994.
Pan Hong 1,  Taoyang Xu 2,  Jiaojiao Xu 2,  Wenyou Chen 3,  Huifang Hu 1,  Jindong Chen 4,  Lan Li 4,  Cancan Zheng 4,  Bin Li 5,  Jun Liu 6,  Wei Dai 7,  Enmin Li 8,  Fan Zhang 9,  Wenwen Xu 10
Affiliations

Affiliations

  • 1 MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China.
  • 2 MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 3 Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • 4 Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 5 State Key Laboratory of Respiratory Disease, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
  • 6 State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 7 Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China.
  • 8 The Key Laboratory of Molecular Biology for the High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China.
  • 9 Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: 875086089@qq.com.
  • 10 MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China; State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China. Electronic address: xuwen6966@163.com.
PMID: 38801885 DOI: 10.1016/j.canlet.2024.216994
Abstract

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.

Keywords

Arf6; CD24; Chemoresistance; Esophageal squamous cell carcinoma; Metastasis.

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