Ribosomal s6 protein kinase 4: a prognostic factor for renal cell carcinoma.
BACKGROUND
The expression and function of ribosomal s6 protein kinase 4 (RSK4) in renal cell carcinoma (RCC) are unknown.


METHODS
Immunohistochemistry was used to detect the expression of RSK4 in RCC, and the relationship between RSK4 expression and clinicopathological features as well as prognosis of RCC patients was statistically analysed. Ectopic RSK4 expression in RCC cell lines was performed to determine its effect on cell cycle regulation, tumour invasiveness, and metastatic capability.


RESULTS
RSK4 was overexpressed in RCCs (P=0.003), compared with normal tissues, and the expression varied in different RCC subtypes (P=0.021), especially in two subtypes of papillary RCCs (P=0.001). RSK4 expression was positively correlated with high pT stage (P<0.001), high Fuhrman grade (P<0.001), lymph node involvement (P<0.001), and presence of distant metastasis (P=0.039), and could predict poor outcome in RCC patients. Molecular studies showed that overexpression of RSK4 could promote cell cycle progression and enhance the invasive and metastatic capability of RCC cell lines and vice versa.


CONCLUSIONS
The expression pattern and molecular mechanisms of RSK4 in RCCs indicate that it could be a potential independent prognostic factor and serve as a new potential therapeutic target for RCC patients.
State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an 710032, China.
L
L
Fan
P
P
Li
Z
Z
Yin
G
G
Fu
D J
DJ
Liao
Y
Y
Liu
J
J
Zhu
Y
Y
Zhang
L
L
Wang
Q
Q
Yan
Y
Y
Guo
C
C
Shao
G
G
Huang
Z
Z
Wang
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D011379:Prognosis; D011621:Pteridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
C516541:BI D1870; D014408:Biomarkers, Tumor; D002070:Butadienes; D004791:Enzyme Inhibitors; D018960:Hyaluronan Receptors; D009570:Nitriles; D011621:Pteridines; D034741:RNA, Small Interfering; C113580:U 0126; C501305:RPS6KA6 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9