title: HCRP-1 regulates cell migration and invasion via EGFR-ERK mediated up-regulation of MMP-2 with prognostic significance in human renal cell carcinoma.
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.
authors: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Feifei
authors: F
authors: Chen
authors: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Urology, Suzhou Municipal Hospital, Suzhou, China.
authors: Junpeng
authors: J
authors: Deng
authors: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Xin
authors: X
authors: Liu
authors: The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Wang
authors: W
authors: Li
authors: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Junnian
authors: J
authors: Zheng
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002681:China / Q000453:epidemiology; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D056827:Endosomal Sorting Complexes Required for Transport; C496437:VPS37A protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2