Overexpression of Cks1 increases the radiotherapy resistance of esophageal squamous cell carcinoma.
OBJECTIVE
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.


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.
Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin, China. wxc3188@126.com
Xiao-Chun
XC
Wang
Li-Li
LL
Tian
Jin
J
Tian
DeGuan
D
Li
YueYing
Y
Wang
HongYing
H
Wu
Hang
H
Zheng
Ai-Min
AM
Meng
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D042846:CDC2-CDC28 Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D045744:Cell Line, Tumor / Q000528:radiation effects; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004790:Enzyme Induction; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D011836:Radiation Tolerance / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014410:Tumor Stem Cell Assay
C093090:CKS1B protein, human; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D042846:CDC2-CDC28 Kinases; D002945:Cisplatin; D005472:Fluorouracil