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

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

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.

Results

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.

Conclusions

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.

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Acknowledgment

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.

Author information

Author notes

  1. Wen-Chin Chiu and Pen-Tzu Fang have contributed equally to this article.

Authors and Affiliations

  1. Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Wen-Chin Chiu PhD, Yu-Han Su MS, Yu-Tong Tsui BS & Shyng-Shiou F. Yuan MD, PhD

  2. Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Wen-Chin Chiu PhD, Pen-Tzu Fang MD & Ming-Yii Huang MD, PhD

  3. Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yi-Chen Lee PhD

  4. School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yen-Yun Wang PhD & Yuk-Kwan Chen MD

  5. Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Stephen Chu-Sung Hu MD, PhD

  6. Division of Oral Pathology and Maxillofacial Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Yuk-Kwan Chen MD

  7. Oral and Maxillofacial Imaging Center, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yuk-Kwan Chen MD

  8. Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan

    Ying-Hsien Kao PhD

  9. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Shyng-Shiou F. Yuan MD, PhD

  10. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Shyng-Shiou F. Yuan MD, PhD

  11. Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan

    Shyng-Shiou F. Yuan MD, PhD

  12. Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Chiao Tung University, Hsinchu, Taiwan

    Shyng-Shiou F. Yuan MD, PhD

  13. Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan

    Shyng-Shiou F. Yuan MD, PhD

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  1. Wen-Chin Chiu PhD
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  2. Pen-Tzu Fang MD
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Correspondence to Ming-Yii Huang MD, PhD or Shyng-Shiou F. Yuan MD, PhD.

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Chiu, WC., Fang, PT., Lee, YC. et al. DNA Repair Protein Rad51 Induces Tumor Growth and Metastasis in Esophageal Squamous Cell Carcinoma via a p38/Akt-Dependent Pathway. Ann Surg Oncol 27, 2090–2101 (2020). https://doi.org/10.1245/s10434-019-08043-x

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