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Published on: September 18, 2013
Expression of RSK4, CD44 and MMP-9 is upregulated and positively correlated in metastatic ccRCC
Jing Ma1, Mingyang Li1, Jia Chai1
1State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, Shaan Xi Province, China.
Background:
To investigate the expression and function of RSK4, MMP-9 and CD44 in primary clear cell renal cell carcinoma (primary ccRCC) and metastatic clear cell renal cell carcinoma (metastatic ccRCC), as well as the correlation with clinicopathological features of patients.
Method:
The expression levels of RSK4, CD44 and MMP-9 in 52 primary ccRCC samples and 48 metastatic ccRCC samples were detected by immunohistochemistry, and the relationship between RSK4, CD44 and MMP-9 expression and clinicopathological features as well as prognosis of metastatic ccRCC patients was statistically analysed. Ectopic RSK4 expression in ccRCC cell lines was performed to determine its effect on cell cycle regulation, tumour invasiveness, and metastatic capability.
Results:
The positive rates of RSK4, MMP-9 and CD44 expression in metastatic ccRCC tissues were 75, 68.75 and 91.7%, respectively, while the rates in primary ccRCC tissues were 44.2, 34.6 and 69.2%, respectively. Thus, the positive rates in metastatic ccRCC were higher than those in primary ccRCC (PRSK4 = 0. 002; PMMP-9 = 0. 002; PCD44 = 0. 001). However, the expression of RSK4, CD44 and MMP-9 was unrelated to age, gender, or metastatic sites (P > 0.05) but was related to WHO/ISUP nucleolar grade (PRSK4 = 0.019; PCD44 = 0.026; PMMP-9 = 0.049). In metastatic ccRCC, expression among the three proteins showed a positive correlation (P = 0.008). Moreover, expression between RSK4 and CD44 (P = 0.019) and MMP-9 and CD44 (P = 0.05) also showed positive correlations, whereas RSK4 and MMP-9 showed no significant correlation (P = 1.00). Molecular studies showed that overexpression of RSK4 could enhance the invasive and migratory abilities of ccRCC cell lines through the regulation of CD44 and MMP-9 expression and vice versa.
Conclusions:
The overexpression of RSK4, MMP-9 and CD44 is associated with the invasion and metastasis of ccRCC, indicating that they could be potential prognostic factors and serve as new potential therapeutic targets for ccRCC.
Insights
Overexpression of RSK4, MMP-9, and CD44 is linked to clear cell renal cell carcinoma (ccRCC) invasion and metastasis. These proteins may serve as prognostic factors and therapeutic targets for ccRCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Clear cell renal cell carcinoma (ccRCC) is a significant health concern.
- Understanding the molecular mechanisms of ccRCC invasion and metastasis is crucial.
Purpose of the Study:
- To investigate the expression of RSK4, MMP-9, and CD44 in primary and metastatic ccRCC.
- To correlate their expression with clinicopathological features and patient prognosis.
- To elucidate the functional role of RSK4 in ccRCC cell behavior.
Main Methods:
- Immunohistochemistry was used to detect RSK4, MMP-9, and CD44 expression in 52 primary and 48 metastatic ccRCC samples.
- Statistical analysis correlated protein expression with clinicopathological features and prognosis.
- In vitro studies examined the effect of RSK4 overexpression on ccRCC cell lines.
Main Results:
- Metastatic ccRCC showed significantly higher positive rates for RSK4, MMP-9, and CD44 compared to primary ccRCC.
- RSK4, MMP-9, and CD44 expression correlated with WHO/ISUP nucleolar grade but not with age, gender, or metastatic sites.
- Positive correlations were observed among RSK4, MMP-9, and CD44 expression in metastatic ccRCC.
- RSK4 overexpression enhanced ccRCC cell invasion and migration by regulating CD44 and MMP-9.
Conclusions:
- Overexpression of RSK4, MMP-9, and CD44 is associated with ccRCC invasion and metastasis.
- These proteins represent potential prognostic factors for ccRCC.
- RSK4, MMP-9, and CD44 are promising therapeutic targets for ccRCC treatment.
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