Cytoplasmic expression of pontin in renal cell carcinoma correlates with tumor invasion, metastasis and patients' survival.
Renal cell carcinoma (RCC) is the most lethal of all genitourinary malignancies. Distant metastasis represents the major cause of death in patients with RCC. Recent studies have implicated the AAA+ ATPase pontin in many cellular activities that are highly relevant to carcinogenesis. In this study, we demonstrate for the first time that pontin was up-regulated in RCC, and plays a previously unknown pro-invasive role in the metastatic progression of RCC through epithelial-to-mesenchymal transition (EMT) pathway. 28 pairs of freshly frozen clear cell RCC samples and the matched normal renal tissues analyzed by quantitative RT-PCR and western blotting demonstrated that pontin was up-regulated in clear cell RCC tissues than in normal renal tissues. In addition, immunohistochemistry was used to evaluate subcellular pontin expression in 95 RCC patients, and found that overexpression of pontin in cytoplasm positively correlated with the metastatic features, predicting unfavorable outcomes of RCC patients. Furthermore, in vitro experiments show pontin was predominantly expressed in cytoplasm of RCC cell lines, and a significant suppression of cell migration and invasion in pontin siRNA treated RCC cell lines was observed. Mechanistic studies show that pontin depletion up-regulated the E-cadherin protein and down-regulated vimentin protein, and decreased nuclear β-catenin expression, suggesting the involvement of EMT in pontin induced metastatic progression. Together, our data suggest pontin as a potential prognostic biomarker in RCC, and provide new promising therapeutic targets for clinical intervention of kidney cancers.
Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Institute of Basic Medical Science and Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Xiang
X
Zhang
Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Institute of Basic Medical Science and Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Juchao
J
Ren
Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Lei
L
Yan
Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Yueqing
Y
Tang
Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Wenhua
W
Zhang
Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Dawei
D
Li
Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Institute of Basic Medical Science and Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Yuanwei
Y
Zang
Central Laboratory, Shandong University Second Hospital, Shandong University, Jinan, Shandong Province, China.
Feng
F
Kong
Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Zhonghua
Z
Xu
D000074183:ATPases Associated with Diverse Cellular Activities; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D016019:Survival Analysis
D015820:Cadherins; D002352:Carrier Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C486549:RUVBL1 protein, human