2. Academic Validation
  3. Targeting EFNA1 suppresses tumor progression via the cMYC-modulated cell cycle and autophagy in esophageal squamous cell carcinoma

Targeting EFNA1 suppresses tumor progression via the cMYC-modulated cell cycle and autophagy in esophageal squamous cell carcinoma

  • Discov Oncol. 2023 May 9;14(1):64. doi: 10.1007/s12672-023-00664-9.
Houxiang Jiang # 1 2,  Shaoxiang Wang # 3,  Ying Liu # 4,  Chaopan Zheng # 5,  Lipeng Chen 4,  Kai Zheng 3,  Zhenyu Xu 6,  Yong Dai 4,  Hongtao Jin 7,  Zhiqiang Cheng 7,  Chang Zou 4 8,  Li Fu 9,  Kaisheng Liu 10,  Xiaoshi Ma 11
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, Anhui, China.
  • 2 Anhui Province Clinical Research Center for Critical Respiratory Medicine, Wuhu, 241001, Anhui, China.
  • 3 School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, China.
  • 4 Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University), Shenzhen, 518020, Guangdong, China.
  • 5 Department of Otolaryngology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University), Shenzhen, 518020, Guangdong, China.
  • 6 Precision Medicine Center, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, Anhui, China.
  • 7 Department of Pathology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University), Shenzhen, 518020, Guangdong, China.
  • 8 School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, 518172, Guangdong, China.
  • 9 Department of Pharmacology, Shenzhen University School of Medicine, Shenzhen, 518060, Guangdong, China. gracelfu@szu.edu.cn.
  • 10 Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University), Shenzhen, 518020, Guangdong, China. liukaisheng@szhospital.com.
  • 11 Department of Urology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University), Shenzhen, 518020, Guangdong, China. ma.xiaoshi@szhospital.com.
  • # Contributed equally.
PMID: 37160815 DOI: 10.1007/s12672-023-00664-9
Abstract

Purpose: Esophageal squamous cell carcinoma (ESCC) remains one of the most common causes of Cancer death due to the lack of effective therapeutic options. New targets and the targeted drugs are required to be identified and developed.

Methods: Highly expressed genes in ESCA were identified using the edgeR package from public datasets. Immunostaining assay verified the high expression level of EFNA1 in ESCC. CCK-8, colony formation and wound healing assays were performed to examine the role of EFNA1 and EphA2 in ESCC progression. Cell cycle was analyzed by flow cytometry and Autophagy activation was determined by autophagolysosome formation using transmission electron microscopy. The small molecule targeting to EFNA1 was identified by molecular docking and the anti-tumor effects were verified by in vitro and in vivo models with radiation treatment.

Results: EFNA1 was highly expressed in esophageal Cancer and significantly associated with poor prognosis. Downregulation of EFNA1 remarkably inhibited cell proliferation and migration. Furthermore, decreased EFNA1 significantly suppressed the expression of cMYC along with its representative downstream genes involved in cell cycle, and activated Autophagy. Similar effects on ESCC progression were obtained from knockdown of the corresponding receptor, EphA2. The potential small molecule targeting to EFNA1, salvianolic acid A (SAA), could significantly suppress ESCC progression and increase the sensitivity to radiotherapy.

Conclusion: We revealed that EFNA1 facilitated the ESCC progression via the possible mechanism of activating cMYC-modulated cell proliferation and suppressing Autophagy, and identified SAA as a potential drug targeting EFNA1, providing new options for the future treatments for ESCC patients.

Keywords

Autophagy; EFNA1; Esophageal squamous cell carcinoma; Salvianolic acid A; cMYC.

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