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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.


Related in: MedlinePlus

Effect of the reduction in HCRP-1 expression on the abilities of cell motility in vitro.(A,B) Forty-eight hours after transfection, the expression of HCRP-1 in the 786-O and OS-RC-2 cells was evaluated by western blotting. β-actin was used as an internal control. (C–F) Cell migration and Matrigel cell invasion assays were performed in 786-O and OS-RC-2 cells after transfection, respectively. Representative fields of migrating or invading cells on the membrane (magnification, ×200). The data are presented as mean ± SD for triplicate determinations. ***P < 0.001.
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f3: Effect of the reduction in HCRP-1 expression on the abilities of cell motility in vitro.(A,B) Forty-eight hours after transfection, the expression of HCRP-1 in the 786-O and OS-RC-2 cells was evaluated by western blotting. β-actin was used as an internal control. (C–F) Cell migration and Matrigel cell invasion assays were performed in 786-O and OS-RC-2 cells after transfection, respectively. Representative fields of migrating or invading cells on the membrane (magnification, ×200). The data are presented as mean ± SD for triplicate determinations. ***P < 0.001.

Mentions: Because low HCRP-1 expression is associated with poor prognosis, supporting HCRP-1 may play an important role in one or more steps of tumor metastasis, we investigated the involvement of HCRP-1 in RCC cells migration and invasion. We failed to construct HCRP-1 plasmid to explore the effect of HCRP-1 on RCC cells migration and invasion. So, we transiently transfected 786-O and OS-RC-2 cells with control siRNA and HCRP-1 siRNA in this study, respectively. Forty-eight hours after transfection, HCRP-1 protein was significantly knockdown in cancer cells (Fig. 3A,B). Transfected cells were subjected to cell migration assay and invasion assay. In cell migration assay, we found that the ability of cell migration was drastically increased after decreased expression of HCRP-1 in both 786-O and OS-RC-2 cells (Fig. 3C,D). In cell invasion assay, the results were corresponded with the cell migration assay, respectively (Fig. 3E,F).


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)

Effect of the reduction in HCRP-1 expression on the abilities of cell motility in vitro.(A,B) Forty-eight hours after transfection, the expression of HCRP-1 in the 786-O and OS-RC-2 cells was evaluated by western blotting. β-actin was used as an internal control. (C–F) Cell migration and Matrigel cell invasion assays were performed in 786-O and OS-RC-2 cells after transfection, respectively. Representative fields of migrating or invading cells on the membrane (magnification, ×200). The data are presented as mean ± SD for triplicate determinations. ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Effect of the reduction in HCRP-1 expression on the abilities of cell motility in vitro.(A,B) Forty-eight hours after transfection, the expression of HCRP-1 in the 786-O and OS-RC-2 cells was evaluated by western blotting. β-actin was used as an internal control. (C–F) Cell migration and Matrigel cell invasion assays were performed in 786-O and OS-RC-2 cells after transfection, respectively. Representative fields of migrating or invading cells on the membrane (magnification, ×200). The data are presented as mean ± SD for triplicate determinations. ***P < 0.001.
Mentions: Because low HCRP-1 expression is associated with poor prognosis, supporting HCRP-1 may play an important role in one or more steps of tumor metastasis, we investigated the involvement of HCRP-1 in RCC cells migration and invasion. We failed to construct HCRP-1 plasmid to explore the effect of HCRP-1 on RCC cells migration and invasion. So, we transiently transfected 786-O and OS-RC-2 cells with control siRNA and HCRP-1 siRNA in this study, respectively. Forty-eight hours after transfection, HCRP-1 protein was significantly knockdown in cancer cells (Fig. 3A,B). Transfected cells were subjected to cell migration assay and invasion assay. In cell migration assay, we found that the ability of cell migration was drastically increased after decreased expression of HCRP-1 in both 786-O and OS-RC-2 cells (Fig. 3C,D). In cell invasion assay, the results were corresponded with the cell migration assay, respectively (Fig. 3E,F).

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