DNA Repair Protein Rad51 Induces Tumor Growth and Metastasis in Esophageal Squamous Cell Carcinoma via a p38/Akt-Dependent Pathway

  • Wen-Chin Chiu
  • Pen-Tzu Fang
  • Yi-Chen Lee
  • Yen-Yun Wang
  • Yu-Han Su
  • Stephen Chu-Sung Hu
  • Yuk-Kwan Chen
  • Yu-Tong Tsui
  • Ying-Hsien Kao
  • Ming-Yii HuangEmail author
  • Shyng-Shiou F. YuanEmail author
Translational Research and Biomarkers



Rad51 is a protein which plays a vital role in DNA double-strand break repair and maintenance of telomeres. However, the underlying mechanism for its action in esophageal squamous cell carcinoma (ESCC) remains unclear.

Patients and Methods

Eighty-seven patients with ESCC were enrolled in this study. Expression of Rad51 in ESCC was determined by immunohistochemistry and correlated with clinicopathological variables by Chi square test. The role of Rad51 in patient survival was determined by Kaplan–Meier estimates. The effects of Rad51 knockdown and overexpression on esophageal cancer growth, migration, and invasion were examined using TE8, CE81T, and KYSE70 cells. The mechanisms involved were also analyzed. Nude mice models were used for assessment of tumor growth.


Rad51 staining was predominantly observed in ESCC patients. ESCC patients with high Rad51 expression had significantly decreased survival (P < 0.001) combined with increased tumor size (P = 0.034) and lymph node metastasis (P = 0.039). Rad51 overexpression promoted, while its knockdown attenuated, esophageal cancer cell viability through cell cycle entry and migration/invasion via epithelial–mesenchymal transition. Moreover, Rad51 overexpression increased colony formation in vitro and tumor growth in vivo. In addition, high Rad51 expression increased cancer progression through the p38/Akt/Snail signaling pathway.


This study indicates a new biological role for Rad51 in ESCC progression. Rad51 may serve as a potential prognostic biomarker and therapeutic target for ESCC patients.



This work was financially supported by grants from Kaohsiung Medical University Research Center Grant (Center for Cancer Research KMU-TC108A04), Kaohsiung Medical University Hospital (KMUH103-3M41, KMUH104-4M46), and the Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.


The authors declare no conflicts of interest.

Supplementary material

10434_2019_8043_MOESM1_ESM.doc (48 kb)
Supplementary material 1 (DOC 47 kb)
10434_2019_8043_MOESM2_ESM.doc (48 kb)
Supplementary material 2 (DOC 48 kb)


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Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  1. 1.Translational Research Center, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
  2. 2.Department of Radiation Oncology, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
  3. 3.Department of Anatomy, School of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  4. 4.School of Dentistry, College of Dental MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  5. 5.Department of Dermatology, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
  6. 6.Division of Oral Pathology and Maxillofacial RadiologyKaohsiung Medical University HospitalKaohsiungTaiwan
  7. 7.Oral and Maxillofacial Imaging Center, College of Dental MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  8. 8.Department of Medical ResearchE-Da HospitalKaohsiungTaiwan
  9. 9.Department of Medical Research, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
  10. 10.Graduate Institute of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  11. 11.Department of Biological Science and Technology, College of Biological Science and TechnologyNational Chiao Tung UniversityHsinchuTaiwan
  12. 12.Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B)National Chiao Tung UniversityHsinchuTaiwan
  13. 13.Center for Cancer ResearchKaohsiung Medical UniversityKaohsiungTaiwan

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