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HCRP-1 regulates cell migration and invasion via EGFR-ERK mediated up-regulation of MMP-2 with prognostic significance in human renal cell carcinoma.

Chen F, Deng J, Liu X, Li W, Zheng J - Sci Rep (2015)

Bottom Line: Treatment with EGFR inhibitor or EGFR siRNA blocked HCRP-1-mediated up-regulation of EGFR, ERK phosphorylation and MMP-2 expression.In summary, our results showed that negative HCRP-1 expression is an independent prognostic factor for RCC patients and promotes migration and invasion by EGFR-ERK-mediated up-regulation of MMP-2.HCRP-1 may serve as a therapeutic target for RCC.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.

ABSTRACT
Previous studies indicated a role of hepatocellular carcinoma-related protein-1(HCRP-1) in human cancers, however, its expression pattern in renal cell carcinoma (RCC) and the molecular mechanism of HCRP-1 on cancer progression have not been characterized. In the present study, HCRP-1 expression was examined in a RCC tissue microarray. The negative expression of HCRP-1 was significantly correlated with tumor grade (P = 0.002), TNM stage (P = 0.001) and pT status (P = 0.003). Furthermore, we showed a strong correlation between negative HCRP-1 expression and worse overall and disease-specific survival (P = 0.0003 and P = 0.0012, respectively). Knockdown of HCRP-1 promoted cell migration and invasion in 786-O and OS-RC-2 cell lines. HCRP-1 depletion increased matrix metalloproteinase (MMP)-2 protein level, with increased extracellular signal-regulatedkinase (ERK) phosphorylation, which could be reversed by ERK siRNA or ERK inhibitor, PD98059. Further analysis showed that HCRP-1 knockdown induced epidermal growth factor receptor (EGFR) phosphorylation. Treatment with EGFR inhibitor or EGFR siRNA blocked HCRP-1-mediated up-regulation of EGFR, ERK phosphorylation and MMP-2 expression. In summary, our results showed that negative HCRP-1 expression is an independent prognostic factor for RCC patients and promotes migration and invasion by EGFR-ERK-mediated up-regulation of MMP-2. HCRP-1 may serve as a therapeutic target for RCC.

No MeSH data available.


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A proposed model of mechanisms involving in siHCRP-1-induced migration and invasion of human RCC cells.
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f9: A proposed model of mechanisms involving in siHCRP-1-induced migration and invasion of human RCC cells.

Mentions: In summary, our results showed that HCRP-1 is under-expressed in RCC and can influence migration and invasion by MMP-2 regulation, which is the result of EGFR-ERK pathway modulation, as is shown in Fig. 9. To our knowledge in this study, HCRP-1 is a novel tumor suppressor gene with an essential role in receptor tyrosine kinase degradation pathway, and could serve as a promising prognostic biomarker for RCC. Nonetheless, the promising role for HCRP-1 in migration and invasion of RCC cells merits further research, which may provide additional insight into its potential as a therapeutic target to decrease metastasis. We also propose further clinical relevance investigation for measuring HCRP-1 expression, to develop a new targeted-therapy to suppress RCC progression.


HCRP-1 regulates cell migration and invasion via EGFR-ERK mediated up-regulation of MMP-2 with prognostic significance in human renal cell carcinoma.

Chen F, Deng J, Liu X, Li W, Zheng J - Sci Rep (2015)

A proposed model of mechanisms involving in siHCRP-1-induced migration and invasion of human RCC cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548257&req=5

f9: A proposed model of mechanisms involving in siHCRP-1-induced migration and invasion of human RCC cells.
Mentions: In summary, our results showed that HCRP-1 is under-expressed in RCC and can influence migration and invasion by MMP-2 regulation, which is the result of EGFR-ERK pathway modulation, as is shown in Fig. 9. To our knowledge in this study, HCRP-1 is a novel tumor suppressor gene with an essential role in receptor tyrosine kinase degradation pathway, and could serve as a promising prognostic biomarker for RCC. Nonetheless, the promising role for HCRP-1 in migration and invasion of RCC cells merits further research, which may provide additional insight into its potential as a therapeutic target to decrease metastasis. We also propose further clinical relevance investigation for measuring HCRP-1 expression, to develop a new targeted-therapy to suppress RCC progression.

Bottom Line: Treatment with EGFR inhibitor or EGFR siRNA blocked HCRP-1-mediated up-regulation of EGFR, ERK phosphorylation and MMP-2 expression.In summary, our results showed that negative HCRP-1 expression is an independent prognostic factor for RCC patients and promotes migration and invasion by EGFR-ERK-mediated up-regulation of MMP-2.HCRP-1 may serve as a therapeutic target for RCC.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.

ABSTRACT
Previous studies indicated a role of hepatocellular carcinoma-related protein-1(HCRP-1) in human cancers, however, its expression pattern in renal cell carcinoma (RCC) and the molecular mechanism of HCRP-1 on cancer progression have not been characterized. In the present study, HCRP-1 expression was examined in a RCC tissue microarray. The negative expression of HCRP-1 was significantly correlated with tumor grade (P = 0.002), TNM stage (P = 0.001) and pT status (P = 0.003). Furthermore, we showed a strong correlation between negative HCRP-1 expression and worse overall and disease-specific survival (P = 0.0003 and P = 0.0012, respectively). Knockdown of HCRP-1 promoted cell migration and invasion in 786-O and OS-RC-2 cell lines. HCRP-1 depletion increased matrix metalloproteinase (MMP)-2 protein level, with increased extracellular signal-regulatedkinase (ERK) phosphorylation, which could be reversed by ERK siRNA or ERK inhibitor, PD98059. Further analysis showed that HCRP-1 knockdown induced epidermal growth factor receptor (EGFR) phosphorylation. Treatment with EGFR inhibitor or EGFR siRNA blocked HCRP-1-mediated up-regulation of EGFR, ERK phosphorylation and MMP-2 expression. In summary, our results showed that negative HCRP-1 expression is an independent prognostic factor for RCC patients and promotes migration and invasion by EGFR-ERK-mediated up-regulation of MMP-2. HCRP-1 may serve as a therapeutic target for RCC.

No MeSH data available.


Related in: MedlinePlus