4.3 Article

Overexpression of Cks1 Increases the Radiotherapy Resistance of Esophageal Squamous Cell Carcinoma

Journal

JOURNAL OF RADIATION RESEARCH
Volume 53, Issue 1, Pages 72-78

Publisher

OXFORD UNIV PRESS
DOI: 10.1269/jrr.11090

Keywords

Cks1; Overexpression; Prognosis; Radiation resistance; ESCC

Funding

  1. National Natural Science Foundation of China [30901723]
  2. Natural Science Foundation of Tianjin [11JCYBJC13700]
  3. Research Fund for the Doctoral Program of Higher Education of China [200800231052]
  4. Institute fund of Radiation Medicine [SF1103, 1106]

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Purposes The Cks1 protein is a member of the highly conserved family of Cks/Suc1 proteins, which interact with Cdks, and was found to be an essential cofactor for efficient Skp2-dependent ubiquitination of p27. The present study was undertaken to examine the expression status of Cks1 in esophageal squamous cell carcinoma and its significance. Materials and Methods The expression of Cks1 in 140 esophageal squamous cell carcinoma patients was examined by immunohistochemistry. The correlations between Cks1 expression and tumor clinicopathologic features were analyzed. The effects of Cks1 expression on radiotherapy results were also examined. Results In the present study, we found that Cks1 is overexpressed in esophageal squamous cell carcinoma tissues. Elevated expression of Cks1 correlates significantly with tumor stage and positive lymph node metastasis (p < 0.05). Moreover, a significant negative correlation was found between Cks1 expression and the survival of patients who received radiotherapy (p < 0.05). At the molecular level, forced expression of Cks1 promotes the radio-resistance ability of EC9706 cells. Knockdown of Cks1 expression sensitizes cancer cells to radiation, and a wobble mutant of Cks1 that is resistant to Cks1 siRNA can rescue this effect. Conclusions These results demonstrate for the first time that overexpression of Cks1 correlates with the increased radiotherapy resistance of esophageal squamous cell carcinoma.

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